AFP011009

General Information

Protein Name Ice-structuring protein A
UniProt ID P04002
Nucleotide Sequence ID in NCBI L00138
Protein Sequence ID in NCBI AAB59964.1
Species Pseudopleuronectes americanus (Winter flounder) (Pleuronectes americanus)
Sequence Length 37
Sequence
Structure PDB ID: 1wfa
Solvent Accessible Surface Area Total SASA 3787.99 Ų Polar SASA 1576.47 Ų Apolar SASA 5364.46 Ų

AFP011009000

Mutation Wild Type
Sequence
Ice crystal morphology
PMID 9398184
DOI 10.1021/bi970817d
Protein Name winter flounder AFP HPLC-6(wild type Thr)
Ice crystal morphology Fig.4 Video microscopy of ice crystals in the presence of type I AFP and variants. Ice crystals were formed in the presence of 1 mg/mL peptide (or 16 mg/mL for LSAAN) in 0.1 M NH4HCO3 (pH 7.9) with an undercooling of 0.1 ℃. Still images at the start (0 min) and the end (10 min) of the undercooling trial are shown for the wild-type (Thr), LSAAN (Ser), and LVAAN (Val) protein.
Ice crystal morphology
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TTTT)
Ice crystal morphology Fig.3 Still images of ice crystals grown from solutions of (a) TTTT (~5mg mL-1), (b) TTTT2KE (4 mg mL-1), (c) VVVV2KE34 (10 mg mL-1), and (d) AAAA2KE (5 mg mL-1). Video microscopy of ice crystals in the absence and presence of antifreeze proteins: (e) GGGG2KE (10 mg mL-1), (f) TTTT2KE (4 mg mL-1), (g) VVVV2KE (10 mg mL-1). Still images are taken at regular intervals over a period of 1 min.
Ice crystal morphology
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAN)
Ice crystal morphology Fig.4 Ice crystal morphologies of type I AFP mutants. Ice crystals were formed in the presence of approximately 1 mg/mL variant AFPs at 0.1 ℃ cooling.
Ice crystal morphology
PMID 20936690
DOI 10.1002/pro.516
Protein Name winter flounder AFP rHPLC6
Ice crystal morphology Fig.1 Activity of rHPLC6 and mutant constructs. (A) Ice crystal morphology of the four proteins in the thermal hysteretic gap. The identity of the protein is indicated below each photograph. The scale bar is the equivalent of 25 μm in length for all photographs.
Ice crystal morphology
PMID 20936690
DOI 10.1002/pro.516
Protein Name winter flounder rHPLC6-Arg37
Ice crystal morphology Fig.1 Activity of rHPLC6 and mutant constructs. (A) Ice crystal morphology of the four proteins in the thermal hysteretic gap. The identity of the protein is indicated below each photograph. The scale bar is the equivalent of 25 μm in length for all photographs.
Ice crystal morphology
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6
Ice crystal morphology Fig.2.B photo images of an ice crystal confined by the wild-type type-I AFP at a concentration of 6.0 mg/ml, undergoing decreases in temperature from -0.09, to -0.64 and to -0.65 °C, respectively, from the left to right (the darker circles in the photo images represent air bubbles in the water and the solution).
Ice crystal morphology
PMID 8762146
DOI 10.1002/pro.5560050617
Protein Name winter flounder AFP HPLC-6
Ice crystal morphology "The ice crystal morphology seen in the presence of AFP9 was that of a hexagonal bipyramid (not shown)."
Ice crystal morphology
PMID 37956730
DOI 10.1016/j.bbapap.2023.140973
Protein Name winter flounder AFP6
Ice crystal morphology Fig.2 Antifreeze activity of E. coli-expressed proteins. Panel A. Ice crystals formed in the presence of 1.5 mM His-SUMO, MutAFP6, His-SUMO-AFP6 and AFP6 in 10 mM NH4HCO3 and buffer alone. Images are labeled with the protein name, or buffer for the buffer control. Each is representative of crystals in a minimum of 3 samples. The white line in each image represents 50 μm.
Ice crystal morphology
PMID 37956730
DOI 10.1016/j.bbapap.2023.140973
Protein Name winter flounder His-SUMO-AFP6
Tag Hexahistidine-SUMO
Ice crystal morphology Fig.2 Antifreeze activity of E. coli-expressed proteins. Panel A. Ice crystals formed in the presence of 1.5 mM His-SUMO, MutAFP6, His-SUMO-AFP6 and AFP6 in 10 mM NH4HCO3 and buffer alone. Images are labeled with the protein name, or buffer for the buffer control. Each is representative of crystals in a minimum of 3 samples. The white line in each image represents 50 μm.
Ice crystal morphology
PMID 9565593
DOI 10.1074/jbc.273.19.11714
Protein Name winter flounder Type I AFP
Ice crystal morphology Fig.4.A Ice crystal morphology. A, ice crystals formed in the presence of WT (a), 15EK (b), Ac-15-KE (c), 15KE (d), and 15EKlac (e and f). The peptide nomenclature is that used in Fig. 1. B, time lapse analysis of ice crystal growth in the presence of 15EKlac, where a, b, and c were recorded at 1, 5, and 10 min, respectively.
Ice crystal morphology
PMID 30760774
DOI 10.1038/s41598-018-36546-2
Protein Name winter flounder AFPI
Ice crystal morphology Fig.4.B Morphology of ice crystals observed for AFPI-III, A20L, and Tis8 at concentrations lower than their IRI endpoint. The hexagonal ice plate is created in the solutions of AFPI-AFPIII and A20L, while it is not facetted for Tis8 and similarly for the solvent (40% sucrose).
Thermal Hysteresis
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP (native winter flounder AFP)
Thermal Hysteresis Fig.2.A The concentration dependence of the antifreeze activity of native and synthetic antifreeze polypeptides. The antifreeze activity was measured using a nanoliterosmometer (Clifton Technical Physics, Hartford, NY). A, native winter flounder AFP; B , Asp1-Arg37;C, Thr2-Arg37; D,Asp5-Arg37.
Thermal Hysteresis
PMID 1765066
DOI 10.1111/j.1432-1033.1991.tb16470.x
Protein Name winter flounder native AFP
Thermal Hysteresis Fig. 5. The concentration dependence of the antifreeze activity ofnative and synthetic unti~reezepolypeptides.The antifreeze activity was measured using a nanoliter osmometer (Clifton Technical Physics, Hartford NY). Peptides were dissolved in the same buffer as Fig. 2, pH 8.5. (●)AFP(KE)2; (○) native AFP.
Thermal Hysteresis
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S00)
Thermal Hysteresis Tab.1 The winter flounder AFP (S00) and six analogs (S04-S40) were synthesized and assayed for antifreeze activity (7), which is defined here as the freezing point depression ofa 1 mM solution relative to that ofSOO. Circulardichroism data showed that all peptides were essentially 100% a-helical (7). Gaps have been placed so as to emphasize the 11-residue repeat sequences. In S00 the Asn (N), Asp (D), and Thr (T) residues, which form the polar face (see Fig. 1 C) ofthe a-helix, are in boldface. All ofthe mutations (underlined) are exchanges oftwo or three amino acids, except for S40, where the Leu residues are replaced by Ala. The bound peptide was energy-minimized as described in Fig. 2, and the computed hydrogen bonds were counted.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(HPLC-6)(S00)
Thermal Hysteresis Fig.3 Dependence of antifreeze activity on AFP concentration. Assays were run in0.1 M ammonium bicarbonate buffer (pH 8.5). Activityisdefinedas the differencebetween the equilibrium melting pointof ice and the freezing point. Thepoor solubilityof SO4 prevented measurementsat higher concentrations.□,SOO; +,S04; ○,S11; ■,S22; x,S23; ◇,S4O; ▲,S12; ●,S21.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(HPLC-6)(S00)
Thermal Hysteresis Tab.2 Relative activitiesof antifreeze peptidesos assessed by different Darameters
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(HPLC-6)(S00)
Thermal Hysteresis Fig.3 Dependence of antifreeze activityon the square root of concentration, using data for Fig. 3.Solid lines are least squares plots of the data; broken lines in D illustrate a plot obtained assuming a two-step binding mechanism.
Thermal Hysteresis
PMID 8433967
DOI 10.1093/protein/6.1.19
Protein Name winter flounder AFP HPLC-6
Thermal Hysteresis Tab.1 AFP sequences with helicity and activity data.
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S00)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Thermal Hysteresis
PMID 9398184
DOI 10.1021/bi970817d
Protein Name winter flounder AFP HPLC-6(wild type Thr)
Thermal Hysteresis Fig.3 Antifreeze activity of type I AFP and its variants. Thermal hysteresis values for LTAAN (O), LVAAN (□), and LSAAN (●) are plotted as a function of concentration in 0.1 M NH4HCO3 (pH 7.9). Each data point represents the mean of at least three determinations. Standard deviations are shown as vertical bars.
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S00)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezing point.
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(TTTT)
Thermal Hysteresis Fig.2.A Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Thermal Hysteresis
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TTTT)
Thermal Hysteresis Fig.1 Measured thermal hysteresis as a function of concentration (a) 0 to 33 mg mL-1; (b) 0 to 6 mg mL-1 for solutions of TTTT (squares), TTTT2KE (diamonds), VVVV2KE (disks), and AAAA2KE (triangles). TTTT data summarized from Duman and DeVries15 is denoted by the solid line. The thin line near zero temperature is the (thermodynamic) colligative depression of the equilibrium freezing point at these concentrations.
Thermal Hysteresis
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP wild-type
Thermal Hysteresis Fig.3. Thermal hysteresis activity as a function of the concentration of A17L (open circles), A19L (closed circles), A20L (open squares), A21L (closed squares) and wild-type (open triangles). Each data point represents the mean of at least three determinations and the vertical bars represent the S.D.
Thermal Hysteresis
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAN)
Thermal Hysteresis Fig.3.A Asn replacement variants: thermal hysteresis activities of wild-type HPLC-6 (LTAAN) (O), variants LTAAT (●), LTAAA (□), LTAAV (■), and LTAAQ (△) were compared over a range of concentrations.
Thermal Hysteresis
PMID 22853917
DOI 10.1016/j.bpj.2012.06.013
Protein Name winter flounder AFP(TATA)
Thermal Hysteresis Fig.1 Freezing point hysteresis in 100 mM NH4HCO3 buffer.TATA (Open diamonds).
Thermal Hysteresis
PMID 28956610
DOI 10.1021/acs.jpcb.7b06619
Protein Name winter flounder AFP HPLC-6
Thermal Hysteresis Fig.2 Thermal hysteresis temperatures of HPLC-6 solution as functions of the AFP concentration with (-) and without (---) including the adsorption orientation. The experimental data2 are shown as ■.
Thermal Hysteresis
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(TTTT)
Thermal Hysteresis Fig.1 Thermal hysteresis as a function of concentration for unbuffered solution of BBBB2KE (filled circles). For comparison, published hysteresis date for the native protein TTTT (open circles) [7] TTTT2KE (diamonds) and hydrophobic analogues VVVV2KE (squares) and AAAA2KE (triangles) [21] are also included.
Thermal Hysteresis
PMID 20936690
DOI 10.1002/pro.516
Protein Name winter flounder AFP rHPLC6
Thermal Hysteresis Fig.1 Activity of rHPLC6 and mutant constructs. (B) Thermal hysteresis measurements. The activities of the constructs were measured using a nanoliter osmometer as described in the Material and Methods section. Synthetic HPLC6, open square; rHPLC6, open circle; rHPLC6-Ala37-NH2, open triangle; rHPLC6-Arg37, solid circle; rHPLC6-Ala37, solid triangle. The lines indicate the average trend for each of the proteins. Synthetic HPLC6 and rHPLC6, solid line; rHPLC6-Ala37-NH2, dotted and dashed line; rHPLC6-Arg37,dashed line; rHPLC6-Ala37, dotted line. The error bars represent the standard deviation of three independent measurements.
Thermal Hysteresis
PMID 20936690
DOI 10.1002/pro.516
Protein Name winter flounder rHPLC6-Arg37
Thermal Hysteresis Fig.1 Activity of rHPLC6 and mutant constructs. (B) Thermal hysteresis measurements. The activities of the constructs were measured using a nanoliter osmometer as described in the Material and Methods section. Synthetic HPLC6, open square; rHPLC6, open circle; rHPLC6-Ala37-NH2, open triangle; rHPLC6-Arg37, solid circle; rHPLC6-Ala37, solid triangle. The lines indicate the average trend for each of the proteins. Synthetic HPLC6 and rHPLC6, solid line; rHPLC6-Ala37-NH2, dotted and dashed line; rHPLC6-Arg37,dashed line; rHPLC6-Ala37, dotted line. The error bars represent the standard deviation of three independent measurements.
Thermal Hysteresis
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6
Thermal Hysteresis Fig.3 Antifreeze activity of the wild-type type-I AFP (black squares), spin-labeled L23C (red discs), spin-labeled L12C (blue, upward-pointing triangles), spin-labeled A20C (purple, downward-pointing triangles), spin-labeled A11C (green diamonds), and spin-labeled A17C (navy blue, leftward-pointing triangles). HPLC6 Wild type (black squares)
Thermal Hysteresis
PMID 8762146
DOI 10.1002/pro.5560050617
Protein Name winter flounder AFP HPLC-6
Thermal Hysteresis Fig.5 Thermal hysteresis activity as a function of AFP concentration. Activity curves for winter flounder HPLC-6 and yellowtail flounder AFP were taken from Scott et al. (1987). Thecurve for AFP9 was based on serial dilutions of a stock 10 mg/mL solution. Each point is the average of at least three determinations.Standard deviations are shown by the vertical bars.
Thermal Hysteresis
PMID 37956730
DOI 10.1016/j.bbapap.2023.140973
Protein Name winter flounder AFP6
Thermal Hysteresis Fig.2 Antifreeze activity of E. coli-expressed proteins. Panel B. Concentration-dependent thermal hysteresis of His-SUMO, MutAFP6, His-SUMO-AFP6 and AFP6. Measurements were performed on each protein and background values for the buffer control were subtracted. Values shown are means ±SD for triplicate samples.
Thermal Hysteresis
PMID 37956730
DOI 10.1016/j.bbapap.2023.140973
Protein Name winter flounder His-SUMO-AFP6
Tag Hexahistidine-SUMO
Thermal Hysteresis Fig.2 Antifreeze activity of E. coli-expressed proteins. Panel B. Concentration-dependent thermal hysteresis of His-SUMO, MutAFP6, His-SUMO-AFP6 and AFP6. Measurements were performed on each protein and background values for the buffer control were subtracted. Values shown are means ±SD for triplicate samples.
Thermal Hysteresis
PMID 8626748
DOI 10.1074/jbc.271.8.4106
Protein Name winter flounder AFP HPLC-6
Thermal Hysteresis Fig.3 The concentration dependence of the antifreeze activities of AFPs isolated from flounder serum and skin. The AFPs are the major serum AFP (HPLC-6) and skin AFPs, sAFP2 and sAFP3.
Thermal Hysteresis
PMID 10686148
DOI 10.1006/prep.1999.1176
Protein Name winter flounder recombinant AFP
Thermal Hysteresis "The antifreeze activity (thermal hysteresis) of the rAFP at 1.5 mM was determined to be 0.67±0.03°C as compared to 0.94±0.02°C for HPLC6."
Thermal Hysteresis
PMID 30760774
DOI 10.1038/s41598-018-36546-2
Protein Name winter flounder AFPI
Thermal Hysteresis Fig.3.C Concentration dependence of thermal hysteresis evaluated for the five AFP samples. The A20L failed to halt the ice crystal growth, for which no TH activity was evaluated.
Thermal Hysteresis
PMID 23860838
DOI 10.1007/s10867-012-9291-7
Protein Name winter flounder AFP HPLC6(type I AFP)
Thermal Hysteresis Fig. 5 Antifreeze activities of type I AFP versus the AFP concentrations
Thermal Hysteresis
PMID 3665937
DOI 10.1111/j.1432-1033.1987.tb13462.x
Protein Name winter flounder AFP A
Thermal Hysteresis Fig.4 Activity curves relating AFP concentrations and thermal hysteresis value. The activity curves for winter flounder (----) and yellowtail flounder (-) AFPs were determined using samples purified from plasma as described by Kao et al. [I7]
Fluorescence-based Ice Plane Affinity
PMID 30760774
DOI 10.1038/s41598-018-36546-2
Protein Name winter flounder AFPI
Fluorescence-based Ice Plane Affinity Fig.5.C The FIPA images captured for the present AFP samples. The images α1–ε1 are the photographs along the c-axis, and α2–δ2 are those normal to the c-axis. The image ε2 shows an oblique view for Tis8. These images are translated to illustrations α3–ε3. The entirely illuminated FIPA pattern (ε1–ε3) was only observed for Tis8.
Ice Recrystallization Inhibition
PMID 30760774
DOI 10.1038/s41598-018-36546-2
Protein Name winter flounder AFPI
Ice Recrystallization Inhibition Fig.2.B Photo examples of time-dependent changes in the ice grains in solvent (40% sucrose) and 1.5 μM solutions of AFPI, AFPII, AFPIII, A20L, and Tis8 at -6℃ , taken from the last 20 min. The scale bars represent 50 μm.
Ice Binding Sites
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S00)
IBS The side chains of Thr (threonine), Asn (asparagine), and Asp (aspartic acid) form hydrogen bonds to the (2 0 2 1) hexagonal bipyramidal plane of ice in a specific pattern.
Ice Binding Sites
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(HPLC-6)(S00)
IBS The potential binding sites are at or near Thr (Thr13, Thr24 etc.) and Asn/Asp residues in the Thr-X-X-Asn/Asp motif.
Ice Binding Sites
PMID 8433967
DOI 10.1093/protein/6.1.19
Protein Name winter flounder AFP HPLC-6
IBS The ice-binding sites mainly involve Thr2, Thr13, Thr24 andThr35.
Ice Binding Sites
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S00)
IBS The charged amino acid residue Asp5 may be involved in binding to the ice surface, and Thr35 is thought to participate in binding of the AFP to the ice surface.
Ice Binding Sites
PMID 9398184
DOI 10.1021/bi970817d
Protein Name winter flounder AFP HPLC-6(wild type Thr)
IBS Putative binding sites are related to Thr and neighboring Asx residues.
Ice Binding Sites
PMID 9414201
DOI 10.1016/S0006-3495(97)78315-2
Protein Name winter flounder AFP
IBS The ice-binding sites can be divided into four regions: Asp-1/Thr-2/Asp-5, Thr-13/Asn-16, Thr-24/Asn-27, and Thr-35/Arg-37. The Thr and Asx (x = p or n) residues in these regions play important roles in ice binding.
Ice Binding Sites
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S00)
IBS The ice-binding sites mainly involve Thr (threonine), Asn (asparagine), and Asp (aspartic acid) residues, which are located at the bottom of the helix.
Ice Binding Sites
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP wild-type
IBS The binding sites involve Thr13, Ala17, Ala21 and equivalent residues at 11-amino-acid intervals along the helix.
Ice Binding Sites
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAN)
IBS The putative ice-binding residues include Thr, Asn, and Leu.
Ice Binding Sites
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6
IBS "It was proposed that the putative ice-binding surface (IBS) comprises the Thr side chains and the conserved i+4 and i+8 Ala side chains, where “i” denotes the positions of the Thr residues"
Ice Binding Sites
PMID 8762146
DOI 10.1002/pro.5560050617
Protein Name winter flounder AFP HPLC-6
IBS The Ice-Binding Site (IBS) may containsT2,D4,T13,N16,T24,N27 and T35.
Ice Binding Sites
PMID 8626748
DOI 10.1074/jbc.271.8.4106
Protein Name winter flounder AFP HPLC-6
IBS Binding sites: Thr, Asn/Asp residues in the motif.
Ice Binding Sites
PMID 9565593
DOI 10.1074/jbc.273.19.11714
Protein Name winter flounder Type I AFP
IBS The putative ice-binding residues (Thr, Asx, and Leu) are aligned and regularly spaced along one face of the helix. Each Thr residue (e.g., Thr-2, Thr-13, Thr-24, and Thr-35) is spaced 11 amino acids (16.5 Å) apart.
Ice Binding Sites
PMID 11509380
DOI 10.1016/S0006-3495(01)75821-3
Protein Name winter flounder AFP
IBS The binding sites involve Thr13, Ala17, Ala21 and equivalent residues at 11-amino-acid intervals along the helix.
Ice Binding Sites
PMID 20453925
DOI 10.1139/O09-183
Protein Name winter flounder AFP HPLC6
IBS The binding sites involve Ala17 and Ala210.
Ice Hemisphere Etching
PMID 2009357
DOI 10.1016/S0006-3495(91)82234-2
Protein Name winter flounder AFP
Ice Hemisphere Etching Fig.2 Photographs of single-crystal hemispheres grown from winter flounder AFP solutions. (a) Bottom view of a hemisphere grown with a prism plane oriented normal to the long axis of the cold finger, scraped and etched. The bright reflections are portions of the ring light reflected from the mirror-smooth, curved ice surface where no antifreeze was incorporated. (b) Side view of a hemisphere growth with [0 0 0 1] oriented parallel to the long axis of cold finger. The tendency toward faceting is clear and corresponds with the etched orientations in (a). The crystallographic orientations of these two hemispheres are the same in the figure, but different with respect to the cold finger axis.
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TTTT)
Ice Hemisphere Etching Fig.4 Top view of oriented single-crystal ice hemispheres grown from 0.03 mg mL-1 solutions of (a) TTTT,19 (b) TTTT2KE, and (c) VVVV2KE34 for comparison (d) AAAA2KE and (e) GGGG2KE. The ice 1h c-axis points vertically up the page. Lighting is provided by two lamps above the hemispheres, seen clearly in (e) the etch-free pattern. Side views of (f) the VVVV2KE hemisphere in panel (c), where straight white lines have been added above the crystal to highlight the distortion of the hemisphere into planes due to the presence of peptide, and (g) the AAAA2KE hemisphere in panel (d).
Ice Grow Rate
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(HPLC-6)(S00)
Ice Grow Rate Fig.5 Ice crystal growth rates in dilute solutions of antifreeze peptides. A, rate of growth along thea axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperatureof ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of 4-6 rate measurements. □,SOO; +, S40; ●,S11; ○,S04; △,S22; ■,S23.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S00)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Ice Grow Rate
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S00)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze peptides. A, rate of growth along the a axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The transition point or threshold is that concentration below which ice crystal growth commences.
Ice plane
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP (native winter flounder AFP)
Ice plane The Ice-plane contains the prism faces and basal planes of ice.
Ice plane
PMID 2009357
DOI 10.1016/S0006-3495(91)82234-2
Protein Name winter flounder AFP
Ice plane The adsorption planes are the 12 equivalent {2 0 2_ 1} bipyramidal planes.
Ice plane
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S00)
Ice plane The Ice-plane contains the {2 0 2_ 1} hexagonal bipyramidal planes. A-helical AFP is along the direction <0 1 1_ 2> on the {2 0 2_ 1} hexagonal bipyramidal planes of ice,
Ice plane
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(HPLC-6)(S00)
Ice plane The AFP probably bind to the pyramidal faces of ice, specifically the (2 0 2_ 1) pyramidal planes.
Ice plane
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S00)
Ice plane It adsorbs to the {2 0 2_ 1}hexagonal bipyramidal planes of ice along the direction <0 1 1_ 2>.
Ice plane
PMID 9398184
DOI 10.1021/bi970817d
Protein Name winter flounder AFP HPLC-6(wild type Thr)
Ice plane The Ice-plane includes the {2 0 2_ 1} binding plane.
Ice plane
PMID 9414201
DOI 10.1016/S0006-3495(97)78315-2
Protein Name winter flounder AFP
Ice plane The Ice-plane contains the {2 0 2_ 1} crystal plane.
Ice plane
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S00)
Ice plane The Ice-plane contains the {2 0 2_ 1} crystal plane.
Ice plane
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(TTTT)
Ice plane The Ice-plane contains the {2 0 2_ 1} hexagonal bipyramidal planes of ice along the [1 1 0 2] direction.
Ice plane
PMID 9688560
DOI 10.1016/s0014-5793(98)00652-8
Protein Name winter flounder AFP(TTTT)
Ice plane Type I antifreeze proteins of winter flounder (including the native protein TTTT and the mutant VVVV2KE) accumulate on the {2 0 2_ 1} plane of ice.
Ice plane
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TTTT)
Ice plane The Ice-plane includes the {2 0 2_ 1} binding plane.
Ice plane
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP wild-type
Ice plane The antifreeze protein binds to the {2 0 2_ 1} hexagonal bipyramidal planes of ice along the <0 1 1_ 2> direction.
Ice plane
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAN)
Ice plane The antifreeze protein binds to the {2 0 2_ 1} hexagonal bipyramidal planes of ice along the <0 1 1_ 2> direction.
Ice plane
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6
Ice plane It binds to the 12 equivalent bipyramidal planes.
Ice plane
PMID 8762146
DOI 10.1002/pro.5560050617
Protein Name winter flounder AFP HPLC-6
Ice plane The {2 0 2_ 1}bipyramidal plane in the direction <0 1 1_ 2>.
Ice plane
PMID 9565593
DOI 10.1074/jbc.273.19.11714
Protein Name winter flounder Type I AFP
Ice plane The antifreeze protein binds to the {2 0 2_ 1} hexagonal bipyramidal planes of ice along the <0 1 1_ 2> direction.
Ice plane
PMID 20453925
DOI 10.1139/O09-183
Protein Name winter flounder AFP HPLC6
Ice plane The antifreeze protein binds to the {2 0 2_ 1} plane.
Ice plane
PMID 30760774
DOI 10.1038/s41598-018-36546-2
Protein Name winter flounder AFPI
Ice plane The adsorption planes are the pyramidal planes.
Brief description
PMID: 2738068
DOI: 10.1016/S0021-9258(18)60466-1
1. The concentration of active polypeptides affected the growth rates of ice along the a and c axes. The a-axis growth rate was inversely proportional to the concentration of active peptides. At low concentrations, the active peptides enhanced c-axis growth, while at high concentrations, they inhibited c-axis growth.At high concentrations, it could hydrogen bond to the basal planes and retard c-axis growth.
2. The results show that AFP adopts an α-helical structure with polar residues (Asp, Thr, Arg) aligned along the helix, which are essential for ice-binding and thermal hysteresis (TH) activity, reaching up to 0.91℃ at 7.00 mM.
3. AFP primarily binds to the prism faces of ice crystals, inhibiting growth along the a-axis at low concentrations and further suppressing c-axis growth at higher concentrations, but does not exhibit ice recrystallization inhibition (IRI) activity.
PMID: 1765066
DOI: 10.1111/j.1432-1033.1991.tb16470.x
1. The antifreeze activity of synthetic AFP(KE)2 with higher α- helicity is the same as that of native AFP, but in terms of affecting ice crystal growth rates, AFP(KE)2 can exert its effects at 7-8 times lower concentrations.
2. The antifreeze activities of both AFP and AFP(KE)2 are pH-dependent, and this dependence is related to the changes in their helix contents.
3. Experiments show that there is a direct but complex relationship between α-helical structure and antifreeze activity. Increasing the α-helix content does not increase the antifreeze activity, but can reduce the AFP concentration required to inhibit ice crystal growth.
4. Both AFP and AFP(KE)2 induce typical hexagonal bipyramidal ice crystal formation without displaying ice recrystallization inhibition (IRI) activity.
PMID: 2009357
DOI: 10.1016/S0006-3495(91)82234-2
1. The antifreeze peptides from winter flounder, Alaskan plaice, and short-horn sculpin adsorb on specific crystal planes of ice. The peptides from winter flounder and Alaskan plaice adsorb on the {2 0 2_ 1} bipyramidal planes, while the peptide from short-horn sculpin adsorbs on the {2 1_ 1_ 0} secondary prism planes.
2. The alignment directions of the three antifreeze peptides on the adsorption planes are probably all [0 1 1_ 2], which is deduced from the elongation directions of the etched regions.
3. There is a structural match between the antifreeze peptide molecules and the ice surface. For example, the 11-amino acid repeat spacing (16.5A) of the antifreeze peptides from winter flounder and Alaskan plaice is close to the 16.7Å repeat spacing in ice along the [0 1 1 2] direction.
PMID: 1489916
DOI: 10.1016/S0006-3495(92)81750-2
1. It is proposed that the antifreeze polypeptide from winter flounder inhibits ice crystal growth by hydrogen bonding of Thr, Asn and Asp side chains to the {2 0 2 1} hexagonal bipyramidal planes of ice in a specific pattern.
2. The binding mode is unidirectional, which increases the packing opportunities of antifreeze polypeptides on the ice surface and thus enhances the activity.
3. Ice crystal growth inhibition occurs through a two-step mechanism involving hydrogen bonding and hydrophobic interpeptide interactions. At low concentrations, it mainly depends on hydrogen bonding and ice crystals grow slowly; at high concentrations, hydrophobic interactions are enhanced and growth is inhibited.
PMID: 1629210
DOI: 10.1016/S0021-9258(19)49684-1
1. This study investigates HPLC-6, a 37-residue antifreeze polypeptide (AFP) from winter flounder (Pseudopleuronectes americanus), and its seven synthetic variants with rearranged neutral and polar amino acids.
2. A specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal antifreeze activity.
3. The development of antifreeze activity is at least a two-stage process. In dilute solution, AFP molecules bind to the ice surface in a specific manner to form hexagonal bipyramidal crystals. At a high enough concentration, the growth of bipyramidal crystals ceases, possibly due to cooperative interactions between helix molecules.
PMID: 8433967
DOI: 10.1093/protein/6.1.19
1. The solution structure of the C-terminal region of the HPLC-6 precursor shows that the spacing between the side chains of Thr2, Thr13, Thr24 and Thr35 can match the repeat distance of oxygen atoms along the [0 1 1_ 2] direction in ice, which is beneficial for binding to the ice lattice.
2. Simulations of two engineered antifreeze protein variants (AFPV1 and AFPV2) showed that their solution structures and activities are consistent with the threonine-ice hydrogen bonding model.
3. AFPV1 had reduced activity due to partial unfolding of the α-helical structure, which increased the spacing between threonine side chains; AFPV2, despite having threonine side chain spacing that matched the ice lattice, had low activity because the bulky side chains of Lys17 and Glu21 interfered with ice binding.
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. Asp1 at the NH2 terminus does not contribute significantly to helix stability and antifreeze activity, but its deletion affects the ice crystal growth curve.
3. The COOH-terminus is relatively sensitive. Replacement of Arg37 by certain amino acids reduces helix content and antifreeze activity.
4. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
5. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.
PMID: 9398184
DOI: 10.1021/bi970817d
1.When the two central threonines in the HPLC-6 isoform of type I antifreeze protein were mutated to serine, the antifreeze activity was almost completely lost; when mutated to valine, only a minor loss of antifreeze activity was observed.
PMID: 9414201
DOI: 10.1016/S0006-3495(97)78315-2
1.The Asp, Asn, and Thr residues of AFP play important roles in ice binding. They can be divided into four ice-binding regions, and the spacing between these regions matches the ice lattice constant, enhancing the ice-binding ability.
2.The correct Thr-Asn distance and sequence are crucial for ice binding. When mutations change this distance and sequence, the antifreeze activity decreases.
PMID: 8344925
DOI: 10.1016/S0021-9258(19)85434-0
1. The native type I antifreeze polypeptide (AFP) from winter flounder is a 37-residue alanine-rich amphiphilic α-helix. It exhibits full antifreeze activity (set as 100% or 0.46°C at 1 mM), with a sharp concentration-dependent transition (threshold ~0.06 mM) between slow ice crystal growth and complete growth arrest.
2. Experimental results show that mutations replacing alanine with glutamine or leucine at certain positions significantly reduce thermal hysteresis (TH) activity, with S51 retaining 73% activity while S52 loses it completely.
3. Structural and ice-binding analyses suggest that these mutations alter protein stability and disrupt its interaction with ice, highlighting the importance of precise residue positioning in AFP function.
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. TTTT exhibits strong antifreeze activity, defined as the difference between the equilibrium melting point and freezing point of the solution.
PMID: 9688560
DOI: 10.1016/s0014-5793(98)00652-8
1. This study investigates the role of threonine residues in the antifreeze activity of a type I antifreeze protein from winter flounder.
2. The valine mutant (VVVV2KE) retained antifreeze activity similar to that of the native antifreeze protein, while the serine mutant (SSSS2KE) and glycine mutant (GGGG2KE) did not show antifreeze activity. This indicates that the threonine hydroxyl groups are not crucial for the accumulation of the native antifreeze protein at the ice/water interface and the inhibition of ice growth.
3. Through the mutation study of the four threonine residues of the type I antifreeze protein from winter flounder, it was found that hydrogen bonding is not necessary for the strong antifreeze action of antifreeze proteins.
DOI: 10.1021/ja9801341
1. Threonine -OH groups are not required for antifreeze activity and hydrogen bonding may not play a crucial role in the ice-binding mechanism of antifreeze proteins.
2. The hydrophobic methyl groups in threonine and valine contribute significantly to antifreeze activity.
3. The native AFP and its mutants preferentially bind to the {2 0 2_ 1} ice plane, while the alanine mutant (AAAA2KE) binds to the {2 1_1_ 0} sculpin plane, highlighting differences in ice interaction. These findings suggest that hydrophobic interactions and specific amino acid substitutions influence ice plane selectivity and antifreeze activity.
PMID: 10601644
DOI: 10.1016/s0014-5793(99)01588-4
1. The traditional ice-binding surface of type I AFP (involving Leu, Asn, and the Thr OH group) may be misidentified. The new binding face encompasses the conserved Ala-rich surface and adjacent Thr.
2. Mutational studies of Ala to Leu in type I AFP showed that the Ala17 mutation (A17L) completely lost antifreeze activity, the Ala21 mutation (A21L) had weak antifreeze activity, and the Ala19 (A19L) and Ala20 (A20L) mutations retained wild-type activity.
3. The γ-gmethyl group of Thr is essential for the ice-binding activity of type I AFP, as demonstrated by the retention of activity in Thr to Val substitutions.
PMID: 10200162
DOI: 10.1021/bi982602p
1. Leu plays a crucial role in preventing the aggregation of alanine-rich helices at in vivo concentrations.
2. Asn may be more important for increasing peptide solubility than for binding to ice through traditional hydrogen bonding and/or steric complementarity.
3. The complete elimination of thermal hysteresis activity after replacing Asn with Gln (LTAAQ) having a larger side chain indicates that Asn may be in contact with the ice surface when type I antifreeze protein binds to the ice lattice.
4. The variant with the introduced ATAAT ice-binding motif (IBM) had higher activity than the wild type when solubility was maintained, but this might be due to the increased number of ice-binding repeats
PMID: 22853917
DOI: 10.1016/j.bpj.2012.06.013
1. The pseudo-wild-type TATW and its three mutants TLTW, SASW , VAVW of winter flounder antifreeze peptide (wf-AFP1) were synthesized, and their thermal hysteresis activities were determined by freezing point hysteresis experiments. The activity ranking was found to be TATA>TATW>VAVA>VAVW>WLTW>SASW.
2. Circular dichroism (CD) experiments SASW showed that although had a high helix content at room temperature, its activity was low. The helix content of TATW, TLTW , and VAVA increased at and their activities were higher than that of SASW, indicating that a large helix content does not guarantee activity.
3. Short-range ice binding and long-range solvent perturbation are two mechanisms related to the activity of antifreeze proteins and glycoproteins.The results showed that the short-range model can explain the activity of mutants, while the long-range model is a necessary condition for activity, as the most active peptides all have an extended dynamical hydration shell. It seems that antifreeze proteins and glycoproteins have evolved different solutions to the antifreeze problem.
PMID: 28956610
DOI: 10.1021/acs.jpcb.7b06619
1. The influence of the adsorption orientation of type I antifreeze proteins on their thermal hysteresis temperature is significant and cannot be ignored.
2. The influence of the adsorption orientation on the thermal hysteresis effect of AFP9 and HPLC-6 is more obvious than that of AAAA2kE.
PMID: 11240143
DOI: 10.1016/s0014-5793(01)02213-x
1. The γ-methyl group of threonine alone is not sufficient to confer ice-growth inhibition properties. The presence of the OH group and the γ-methyl in TTTT, or an additional methyl group like in VVVV2KE, confers significantly higher thermal hysteresis.
2. The IIII2KE with isoleucine replacing threonine can modify the ice crystal shape but shows no thermal hysteresis, indicating that replacing the hydroxyl group of threonine in TTTT with an ethyl group removes the ability to inhibit ice growth.
3. TTTTAL2KE and VVVVAL2KE with mutations in aspartic acid (Asp) and asparagine (Asn) show no thermal hysteresis, confirming the involvement of these Asx residues in the ice - growth inhibition mechanism.
PMID: 20936690
DOI: 10.1002/pro.516
1. The nonamidated mutants had 35% lower thermal hysteresis (TH) activities compared to the amidated proteins. NMR and circular dichroism analysis showed that all proteins remained α-helical. Relaxation data indicated that the C-terminal residues of nonamidated mutants were more flexible due to the loss of the amide group, while the amidated Ala37 mutant had a rigid C-terminus and high TH activity.
2. The experiment proposes that the increase in the flexibility of AFP causes it to lose activity because its dynamic nature prevents it from strongly binding to the ice surface, and rigidity may be important for AFP to maintain close contact with the rigid ice surface.
PMID: 29487966
DOI: 10.1007/s00249-018-1285-3
1. The putative ice-binding surface (IBS) of type-I AFPs, which consists of Thr side chains and conserved i+4 and i+8 Ala side chains, is crucial for their antifreeze functions.
2. Type-I AFPs can inhibit the nucleation of seed ice crystals, allowing solutions to stay in super-cooled states at lower temperatures.
3. A proposed antifreeze mechanism of AFPs involves the formation of a water-AFP-ice (WAI) interphase, which reduces ice-water interfacial tension, enhances the local colligative effect, and interrupts water molecules from joining the ice lattice.
PMID: 8762146
DOI: 10.1002/pro.5560050617
1. Winter flounder HPLC-6 is a major serum Type I AFP with three 11-amino acid repeats, being alanine-rich, amphipathic and α-helical.
2. It exhibits antifreeze activity via adsorption-inhibition, binding to ice to lower the nonequilibrium freezing point.
PMID: 37956730
DOI: 10.1016/j.bbapap.2023.140973
1. AFP6 can change from an ice nucleation inhibitor to a nucleator as the temperature drops, and this dual-effect is not observed in other tested proteins.
2. AFP6 exhibits strong TH activity and forms bipyramidal ice crystals, while a mutant variant (MutAFP6) with four point mutations (T2S, A17L, T24S, T35S) loses this activity and alters ice crystal morphology.
3. The ice nucleation activity of AFP6 is concentration-dependent, reaching its maximum at 1.5 mM.
4. The fusion protein of AFP6, His-SUMO-AFP6, has thermal hysteresis activity but no ice nucleation activity, indicating that the fusion moiety may inhibit the protein assembly required for AFP6 nucleation.
PMID: 8626748
DOI: 10.1074/jbc.271.8.4106
1. Skin AFPs lack signal peptides and prosequences, suggesting intracellular antifreeze function.
2. Skin AFPs are encoded by a 30-40 copy multigene family, coexisting with liver AFP genes in flounder.
3. Skin AFPs are highly expressed in external tissues (skin, scales, fins, gills), protecting body surfaces from freezing.
PMID: 9565593
DOI: 10.1074/jbc.273.19.11714
1. The wild-type AFP, with a single-helix structure and key threonine residues aligned for ice binding, effectively induces hexagonal bipyramidal ice crystal formation.
2. Shortened 15-residue variants and engineered mutants lacked thermal hysteresis (TH) activity but retained partial ice-binding ability, supporting an "induced-fit" binding model where initial ice interaction occurs progressively.
PMID: 11509380
DOI: 10.1016/S0006-3495(01)75821-3
1. Some researchers have proposed that the ice-binding face of type I antifreeze protein consists of Ala17, Ala21, the γ-methyl of Thr13, and equivalent residues at 11-amino-acid intervals. However, the specific binding sites are still not very clear.
2. Mutation experiments show that the change of some amino acid residues will affect the antifreeze activity, suggesting that the regions near these residues are related to ice binding.
PMID: 10686148
DOI: 10.1006/prep.1999.1176
1. Successfully constructed the winter flounder HPLC6 secretory expression plasmid and expressed the recombinant AFP (rAFP) in Escherichia coli.
2. The recombinant antifreeze protein (rAFP) was efficiently excreted into the culture medium, with a yield of about 16 mg/L after 18 hours of induction.
3. The rAFP without C-terminal amidation was about 70% active compared to the amidated wild-type protein, indicating the importance of the C-terminal cap structure in protein stability and function.
PMID: 20453925
DOI: 10.1139/O09-183
1. Type I AFPs are rich in alanine and mainly α-helical, and different isoforms have distinct structures.
2. For HPLC6, mutation studies have found that alanine and threonine methyl participate in the formation of ice binding surfaces, rather than the hydrogen bonding of threonine hydroxyl groups;
3. The discontinuous multi alanine fragment of hyp type I may enable it to bind to multiple ice planes, thus exhibiting hyperactive activity, but the exact ice binding site has not been determined through mutation analysis.
PMID: 30760774
DOI: 10.1038/s41598-018-36546-2
1. There is no obvious correlation between thermal hysteresis activity and ice recrystallization inhibition activity. For example, the thermal hysteresis values of AFP II and AFP III are similar, but their ice recrystallization inhibition efficiencies are significantly different.
2. Antifreeze proteins can change the morphology of ice crystals. Low concentrations of antifreeze proteins can trigger ice recrystallization inhibition activity, and high concentrations are not necessary. Excess antifreeze proteins may be harmful.
PMID: 23860838
DOI: 10.1007/s10867-012-9291-7
1. This study investigates the type I antifreeze protein (AFP) HPLC-6 from Pseudopleuronectes americanus (Winter flounder) using NMR microimaging to analyze its ice-binding and antifreeze mechanisms.
2. The results show that HPLC-6 AFP induces localized ice melting, maintains a supercooled water phase, and inhibits ice recrystallization, contributing to its thermal hysteresis (TH) activity of up to 0.56℃ at 5.0 mg/mL.
PMID: 3665937
DOI: 10.1111/j.1432-1033.1987.tb13462.x
1. The cDNA encoding the major serum antifreeze protein in the yellowtail flounder was cloned, and its sequence shows differences from the winter flounder AFP, including an additional 11-amino-acid repeat and fewer hydrophilic ice-binding residues.
2. On a mass basis, the yellowtail flounder antifreeze is only 80% as effective as the winter flounder antifreeze at depressing the freezing temperature of aqueous solutions, probably due to the reduced number of hydrophilic ice-binding residues per molecule.
3. Variation in the number of 11-amino-acid repeats in AFPs might arise by unequal crossing over during recombination within the AFP multigene family.

AFP011009001

Mutation 1del
Sequence
Thermal Hysteresis
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP(Thr-Arg)
Thermal Hysteresis Fig.2.C The concentration dependence of the antifreeze activity of native and synthetic antifreeze polypeptides. The antifreeze activity was measured using a nanoliterosmometer (Clifton Technical Physics, Hartford, NY). A, native winter flounder AFP; B , Asp-Arg;C, Thr-Arg; D,Asp-Arg
Ice Grow Rate
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP(Thr-Arg)
Ice Grow Rate Fig.3 Component growth rates of ice in solutions of synthetic antifreeze polypeptide supercooled 0.1 ℃ below the equilibrium melting temperature. A, a axis growth rate; B, c axis growthrate; ●, Asp¹-Arg³⁷; △, Thr²-Arg³⁷; ○, Asp⁵-Arg³⁷.The data paints and error burs represent the means ±S.D. (n=5).
Brief description
PMID: 2738068
DOI: 10.1016/S0021-9258(18)60466-1
1. The concentration of active polypeptides affected the growth rates of ice along the a and c axes. The a-axis growth rate was inversely proportional to the concentration of active peptides. At low concentrations, the active peptides enhanced c-axis growth, while at high concentrations, they inhibited c-axis growth. At high concentrations, it could hydrogen bond to the basal planes and retard c-axis growth.
2. The results show that AFP adopts an α-helical structure with polar residues (Asp, Thr, Arg) aligned along the helix, which are essential for ice-binding and thermal hysteresis (TH) activity, reaching up to 0.91℃ at 7.00 mM.
3. AFP primarily binds to the prism faces of ice crystals, inhibiting growth along the a-axis at low concentrations and further suppressing c-axis growth at higher concentrations, but does not exhibit ice recrystallization inhibition (IRI) activity.

AFP011009002

Mutation 1_4del
Sequence
Thermal Hysteresis
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP(Asp-Arg)
Thermal Hysteresis Fig.2.D The concentration dependence of the antifreeze activity of native and synthetic antifreeze polypeptides. The antifreeze activity was measured using a nanoliterosmometer (Clifton Technical Physics, Hartford, NY). A, native winter flounder AFP; B , Asp-Arg;C, Thr-Arg; D,Asp-Arg
Ice Grow Rate
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP(Asp-Arg)
Ice Grow Rate Fig.3 Component growth rates of ice in solutions of synthetic antifreeze polypeptide supercooled 0.1 ℃ below the equilibrium melting temperature. A, a axis growth rate; B, c axis growthrate; ●, Asp¹-Arg³⁷; △, Thr²-Arg³⁷; ○, Asp⁵-Arg³⁷.The data paints and error burs represent the means ±S.D. (n=5).
Brief description
PMID: 2738068
DOI: 10.1016/S0021-9258(18)60466-1
1. The concentration of active polypeptides affected the growth rates of ice along the a and c axes. The a-axis growth rate was inversely proportional to the concentration of active peptides. At low concentrations, the active peptides enhanced c-axis growth, while at high concentrations, they inhibited c-axis growth. At high concentrations, it could hydrogen bond to the basal planes and retard c-axis growth.
2. The results show that AFP adopts an α-helical structure with polar residues (Asp, Thr, Arg) aligned along the helix, which are essential for ice-binding and thermal hysteresis (TH) activity, reaching up to 0.91℃ at 7.00 mM.
3. AFP primarily binds to the prism faces of ice crystals, inhibiting growth along the a-axis at low concentrations and further suppressing c-axis growth at higher concentrations, but does not exhibit ice recrystallization inhibition (IRI) activity.

AFP011009003

Mutation A11E,1_10del
Sequence
Thermal Hysteresis
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP(GluLeu-Arg)
Thermal Hysteresis "while all the other smaller peptides (Table I) exhibited no antifreeze activity."
Brief description
PMID: 2738068
DOI: 10.1016/S0021-9258(18)60466-1
1. The concentration of active polypeptides affected the growth rates of ice along the a and c axes. The a-axis growth rate was inversely proportional to the concentration of active peptides. At low concentrations, the active peptides enhanced c-axis growth, while at high concentrations, they inhibited c-axis growth. At high concentrations, it could hydrogen bond to the basal planes and retard c-axis growth.
2. The results show that AFP adopts an α-helical structure with polar residues (Asp, Thr, Arg) aligned along the helix, which are essential for ice-binding and thermal hysteresis (TH) activity, reaching up to 0.91℃ at 7.00 mM.
3. AFP primarily binds to the prism faces of ice crystals, inhibiting growth along the a-axis at low concentrations and further suppressing c-axis growth at higher concentrations, but does not exhibit ice recrystallization inhibition (IRI) activity.

AFP011009004

Mutation 1_11del
Sequence
Thermal Hysteresis
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP(Leu-Arg)
Thermal Hysteresis "while all the other smaller peptides (Table I) exhibited no antifreeze activity."
Brief description
PMID: 2738068
DOI: 10.1016/S0021-9258(18)60466-1
1. The concentration of active polypeptides affected the growth rates of ice along the a and c axes. The a-axis growth rate was inversely proportional to the concentration of active peptides. At low concentrations, the active peptides enhanced c-axis growth, while at high concentrations, they inhibited c-axis growth. At high concentrations, it could hydrogen bond to the basal planes and retard c-axis growth.
2. The results show that AFP adopts an α-helical structure with polar residues (Asp, Thr, Arg) aligned along the helix, which are essential for ice-binding and thermal hysteresis (TH) activity, reaching up to 0.91℃ at 7.00 mM.
3. AFP primarily binds to the prism faces of ice crystals, inhibiting growth along the a-axis at low concentrations and further suppressing c-axis growth at higher concentrations, but does not exhibit ice recrystallization inhibition (IRI) activity.

AFP011009005

Mutation 1_21del
Sequence
Thermal Hysteresis
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP(Glu-Arg)
Thermal Hysteresis "while all the other smaller peptides (Table I) exhibited no antifreeze activity."
Brief description
PMID: 2738068
DOI: 10.1016/S0021-9258(18)60466-1
1. The concentration of active polypeptides affected the growth rates of ice along the a and c axes. The a-axis growth rate was inversely proportional to the concentration of active peptides. At low concentrations, the active peptides enhanced c-axis growth, while at high concentrations, they inhibited c-axis growth. At high concentrations, it could hydrogen bond to the basal planes and retard c-axis growth.
2. The results show that AFP adopts an α-helical structure with polar residues (Asp, Thr, Arg) aligned along the helix, which are essential for ice-binding and thermal hysteresis (TH) activity, reaching up to 0.91℃ at 7.00 mM.
3. AFP primarily binds to the prism faces of ice crystals, inhibiting growth along the a-axis at low concentrations and further suppressing c-axis growth at higher concentrations, but does not exhibit ice recrystallization inhibition (IRI) activity.

AFP011009006

Mutation 1_22del
Sequence
Thermal Hysteresis
PMID 2738068
DOI 10.1016/S0021-9258(18)60466-1
Protein Name winter flounder AFP(Leu-Arg)
Thermal Hysteresis "while all the other smaller peptides (Table I) exhibited no antifreeze activity."
Brief description
PMID: 2738068
DOI: 10.1016/S0021-9258(18)60466-1
1. The concentration of active polypeptides affected the growth rates of ice along the a and c axes. The a-axis growth rate was inversely proportional to the concentration of active peptides. At low concentrations, the active peptides enhanced c-axis growth, while at high concentrations, they inhibited c-axis growth. At high concentrations, it could hydrogen bond to the basal planes and retard c-axis growth.
2. The results show that AFP adopts an α-helical structure with polar residues (Asp, Thr, Arg) aligned along the helix, which are essential for ice-binding and thermal hysteresis (TH) activity, reaching up to 0.91℃ at 7.00 mM.
3. AFP primarily binds to the prism faces of ice crystals, inhibiting growth along the a-axis at low concentrations and further suppressing c-axis growth at higher concentrations, but does not exhibit ice recrystallization inhibition (IRI) activity.

AFP011009007

Mutation A7K,A11E,A29K,A33E
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TTTT2KE)
Ice crystal morphology Fig.3 Still images of ice crystals grown from solutions of (a) TTTT (~5mg mL-1), (b) TTTT2KE (4 mg mL-1), (c) VVVV2KE34 (10 mg mL-1), and (d) AAAA2KE (5 mg mL-1). Video microscopy of ice crystals in the absence and presence of antifreeze proteins: (e) GGGG2KE (10 mg mL-1), (f) TTTT2KE (4 mg mL-1), (g) VVVV2KE (10 mg mL-1). Still images are taken at regular intervals over a period of 1 min.
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P9
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID 1765066
DOI 10.1111/j.1432-1033.1991.tb16470.x
Protein Name winter flounder AFP(KE2)
Thermal Hysteresis Fig. 5. The concentration dependence of the antifreeze activity ofnative and synthetic unti~reezepolypeptides.The antifreeze activity was measured using a nanoliter osmometer (Clifton Technical Physics, Hartford NY). Peptides were dissolved in the same buffer as Fig. 2, pH 8.5. (●)AFP(KE)2; (○) native AFP.
Thermal Hysteresis
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TTTT2KE)
Thermal Hysteresis Fig.1 Measured thermal hysteresis as a function of concentration (a) 0 to 33 mg mL-1; (b) 0 to 6 mg mL-1 for solutions of TTTT (squares), TTTT2KE (diamonds), VVVV2KE (disks), and AAAA2KE (triangles). TTTT data summarized from Duman and DeVries15 is denoted by the solid line. The thin line near zero temperature is the (thermodynamic) colligative depression of the equilibrium freezing point at these concentrations.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P9
Thermal Hysteresis "P9 exhibits a true antifreeze hysteresis activity (thermal hysteresis = 0.52 °C at 4 mg/mL)."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TTTT2KE)
Ice Hemisphere Etching Fig.4 Top view of oriented single-crystal ice hemispheres grown from 0.03 mg mL-1 solutions of (a) TTTT,19 (b) TTTT2KE, and (c) VVVV2KE34 for comparison (d) AAAA2KE and (e) GGGG2KE. The ice 1h c-axis points vertically up the page. Lighting is provided by two lamps above the hemispheres, seen clearly in (e) the etch-free pattern. Side views of (f) the VVVV2KE hemisphere in panel (c), where straight white lines have been added above the crystal to highlight the distortion of the hemisphere into planes due to the presence of peptide, and (g) the AAAA2KE hemisphere in panel (d).
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P9
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Ice plane
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TTTT2KE)
Ice plane The Ice-plane includes the {2 0 2_ 1} binding plane.
Brief description
PMID: 1765066
DOI: 10.1111/j.1432-1033.1991.tb16470.x
1. The antifreeze activity of synthetic AFP(KE)2 with higher α- helicity is the same as that of native AFP, but in terms of affecting ice crystal growth rates, AFP(KE)2 can exert its effects at 7-8 times lower concentrations.
2. The antifreeze activities of both AFP and AFP(KE)2 are pH-dependent, and this dependence is related to the changes in their helix contents.
3. Experiments show that there is a direct but complex relationship between α-helical structure and antifreeze activity. Increasing the α-helix content does not increase the antifreeze activity, but can reduce the AFP concentration required to inhibit ice crystal growth.
4. Both AFP and AFP(KE)2 induce typical hexagonal bipyramidal ice crystal formation without displaying ice recrystallization inhibition (IRI) activity.
DOI: 10.1021/ja9801341
1. Threonine -OH groups are not required for antifreeze activity and hydrogen bonding may not play a crucial role in the ice-binding mechanism of antifreeze proteins.
2. The hydrophobic methyl groups in threonine and valine contribute significantly to antifreeze activity.
3. The native AFP and its mutants preferentially bind to the {2 0 2_ 1} ice plane, while the alanine mutant (AAAA2KE) binds to the {2 1_1_ 0} sculpin plane, highlighting differences in ice interaction. These findings suggest that hydrophobic interactions and specific amino acid substitutions influence ice plane selectivity and antifreeze activity.
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.

AFP011009008

Mutation Designed
Sequence
Ice Recrystallization Inhibition
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa2
Tag SPA
Ice Recrystallization Inhibition Fig.5 Recrystallization inhibition by chimeric proteins. The first row shows RI assays on dilutions of the Spa-X negative control. Theremaining rows each show dilutions of a particular chimeric protein (e.g. the row labeled Afa3 contains dilutions of Spa-Afa3), and the protein-free control that was conducted simultaneously. The columns (A-F) represent the following results, for each protein: B, the highest dilution showing complete RI; A, the next lower dilution relative to B; C, the next higher dilution relative to B ; D , the highest dilution showing clear partial RI; E,a higher dilution, not showing detectable RI; F,the control conducted simultaneously with A-E, using dilution buffer only. Each photograph shows a 520-pm hy 330-μm area of the appropriate frozen droplet. The dilution represented hy a photograph is shown helow it as a power of 2, e.g. at bottom left "-6" indicates the 2-6 dilution.
Ice Recrystallization Inhibition
PMID 8477839
DOI 10.1016/0014-5793(93)80090-H
Protein Name antifreeze analogue Afa2
Ice Recrystallization Inhibition Tab III Titration of recrystallization inhibition activities of free Afa peptides.
Brief description
PMID: 2019569
DOI: 10.1016/S0021-9258(20)89451-4
1. Chimeric proteins containing antifreeze domains can inhibit ice recrystallization, and the IRI activity varies with the number of 11-amino-acid repeats in the antifreeze moiety.
2. The salt bridge and carboxyl-terminal arginine in the antifreeze protein seem to have a certain synergy effect on the IRI activity.
3. Proteins with two 11-amino-acid repeats lack significant IRI activity, while those with three, four, and five repeats show increasing inhibitory activities.
PMID: 8477839
DOI: 10.1016/0014-5793(93)80090-H
1. Antifreeze peptides require a minimum of three TA??A6? repeats (≥37 aa) to exhibit ice recrystallization inhibition activity; the two-repeat variant (Afa2) showed no activity even at high concentrations.
2. Increased peptide length enhances antifreeze potency; Afa4 (48 aa) and Afa5 (59 aa) showed lower MIC values (3–9 μg/ml) compared to shorter variants like Afa3 (12–40 μg/ml), indicating stronger recrystallization inhibition.
3. Engineered peptides lack C-terminal amidation, a key modification in natural antifreeze peptides, potentially explaining their reduced activity compared to native counterparts.

AFP011009009

Mutation Designed
Sequence
Ice Recrystallization Inhibition
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa3
Tag SPA
Ice Recrystallization Inhibition Fig.5 Recrystallization inhibition by chimeric proteins. The first row shows RI assays on dilutions of the Spa-X negative control. Theremaining rows each show dilutions of a particular chimeric protein (e.g. the row labeled Afa3 contains dilutions of Spa-Afa3), and the protein-free control that was conducted simultaneously. The columns (A-F) represent the following results, for each protein: B, the highest dilution showing complete RI; A, the next lower dilution relative to B; C, the next higher dilution relative to B ; D , the highest dilution showing clear partial RI; E,a higher dilution, not showing detectable RI; F,the control conducted simultaneously with A-E, using dilution buffer only. Each photograph shows a 520-pm hy 330-μm area of the appropriate frozen droplet. The dilution represented hy a photograph is shown helow it as a power of 2, e.g. at bottom left "-6" indicates the 2-6 dilution.
Ice Recrystallization Inhibition
PMID 8477839
DOI 10.1016/0014-5793(93)80090-H
Protein Name antifreeze analogue Afa3
Ice Recrystallization Inhibition Tab III Titration of recrystallization inhibition activities of free Afa peptides.
Brief description
PMID: 2019569
DOI: 10.1016/S0021-9258(20)89451-4
1. Chimeric proteins containing antifreeze domains can inhibit ice recrystallization, and the IRI activity varies with the number of 11-amino-acid repeats in the antifreeze moiety.
2. The salt bridge and carboxyl-terminal arginine in the antifreeze protein seem to have a certain synergy effect on the IRI activity.
3. Proteins with two 11-amino-acid repeats lack significant IRI activity, while those with three, four, and five repeats show increasing inhibitory activities.
PMID: 8477839
DOI: 10.1016/0014-5793(93)80090-H
1. Antifreeze peptides require a minimum of three TA??A6? repeats (≥37 aa) to exhibit ice recrystallization inhibition activity; the two-repeat variant (Afa2) showed no activity even at high concentrations.
2. Increased peptide length enhances antifreeze potency; Afa4 (48 aa) and Afa5 (59 aa) showed lower MIC values (3–9 μg/ml) compared to shorter variants like Afa3 (12–40 μg/ml), indicating stronger recrystallization inhibition.
3. Engineered peptides lack C-terminal amidation, a key modification in natural antifreeze peptides, potentially explaining their reduced activity compared to native counterparts.

AFP011009010

Mutation Designed
Sequence
Ice Recrystallization Inhibition
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa3R
Tag SPA
Ice Recrystallization Inhibition Fig.5 Recrystallization inhibition by chimeric proteins. The first row shows RI assays on dilutions of the Spa-X negative control. Theremaining rows each show dilutions of a particular chimeric protein (e.g. the row labeled Afa3 contains dilutions of Spa-Afa3), and the protein-free control that was conducted simultaneously. The columns (A-F) represent the following results, for each protein: B, the highest dilution showing complete RI; A, the next lower dilution relative to B; C, the next higher dilution relative to B ; D , the highest dilution showing clear partial RI; E,a higher dilution, not showing detectable RI; F,the control conducted simultaneously with A-E, using dilution buffer only. Each photograph shows a 520-pm hy 330-μm area of the appropriate frozen droplet. The dilution represented hy a photograph is shown helow it as a power of 2, e.g. at bottom left "-6" indicates the 2-6 dilution.
Ice Recrystallization Inhibition
PMID 8477839
DOI 10.1016/0014-5793(93)80090-H
Protein Name antifreeze analogue Afa3R
Ice Recrystallization Inhibition Tab III Titration of recrystallization inhibition activities of free Afa peptides.
Brief description
PMID: 2019569
DOI: 10.1016/S0021-9258(20)89451-4
1. Chimeric proteins containing antifreeze domains can inhibit ice recrystallization, and the IRI activity varies with the number of 11-amino-acid repeats in the antifreeze moiety.
2. The salt bridge and carboxyl-terminal arginine in the antifreeze protein seem to have a certain synergy effect on the IRI activity.
3. Proteins with two 11-amino-acid repeats lack significant IRI activity, while those with three, four, and five repeats show increasing inhibitory activities.
PMID: 8477839
DOI: 10.1016/0014-5793(93)80090-H
1. Antifreeze peptides require a minimum of three TA??A6? repeats (≥37 aa) to exhibit ice recrystallization inhibition activity; the two-repeat variant (Afa2) showed no activity even at high concentrations.
2. Increased peptide length enhances antifreeze potency; Afa4 (48 aa) and Afa5 (59 aa) showed lower MIC values (3–9 μg/ml) compared to shorter variants like Afa3 (12–40 μg/ml), indicating stronger recrystallization inhibition.
3. Engineered peptides lack C-terminal amidation, a key modification in natural antifreeze peptides, potentially explaining their reduced activity compared to native counterparts.

AFP011009011

Mutation Designed
Sequence
Ice Recrystallization Inhibition
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa3SB/R
Tag SPA
Ice Recrystallization Inhibition Fig.5 Recrystallization inhibition by chimeric proteins. The first row shows RI assays on dilutions of the Spa-X negative control. Theremaining rows each show dilutions of a particular chimeric protein (e.g. the row labeled Afa3 contains dilutions of Spa-Afa3), and the protein-free control that was conducted simultaneously. The columns (A-F) represent the following results, for each protein: B, the highest dilution showing complete RI; A, the next lower dilution relative to B; C, the next higher dilution relative to B ; D , the highest dilution showing clear partial RI; E,a higher dilution, not showing detectable RI; F,the control conducted simultaneously with A-E, using dilution buffer only. Each photograph shows a 520-pm hy 330-μm area of the appropriate frozen droplet. The dilution represented hy a photograph is shown helow it as a power of 2, e.g. at bottom left "-6" indicates the 2-6 dilution.
Ice Recrystallization Inhibition
PMID 8477839
DOI 10.1016/0014-5793(93)80090-H
Protein Name antifreeze analogue Afa3SB/R
Ice Recrystallization Inhibition Tab III Titration of recrystallization inhibition activities of free Afa peptides.
Brief description
PMID: 2019569
DOI: 10.1016/S0021-9258(20)89451-4
1. Chimeric proteins containing antifreeze domains can inhibit ice recrystallization, and the IRI activity varies with the number of 11-amino-acid repeats in the antifreeze moiety.
2. The salt bridge and carboxyl-terminal arginine in the antifreeze protein seem to have a certain synergy effect on the IRI activity.
3. Proteins with two 11-amino-acid repeats lack significant IRI activity, while those with three, four, and five repeats show increasing inhibitory activities.
PMID: 8477839
DOI: 10.1016/0014-5793(93)80090-H
1. Antifreeze peptides require a minimum of three TA??A6? repeats (≥37 aa) to exhibit ice recrystallization inhibition activity; the two-repeat variant (Afa2) showed no activity even at high concentrations.
2. Increased peptide length enhances antifreeze potency; Afa4 (48 aa) and Afa5 (59 aa) showed lower MIC values (3–9 μg/ml) compared to shorter variants like Afa3 (12–40 μg/ml), indicating stronger recrystallization inhibition.
3. Engineered peptides lack C-terminal amidation, a key modification in natural antifreeze peptides, potentially explaining their reduced activity compared to native counterparts.

AFP011009012

Mutation Designed
Sequence
Ice Recrystallization Inhibition
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa3SB
Tag SPA
Ice Recrystallization Inhibition Fig.5 Recrystallization inhibition by chimeric proteins. The first row shows RI assays on dilutions of the Spa-X negative control. Theremaining rows each show dilutions of a particular chimeric protein (e.g. the row labeled Afa3 contains dilutions of Spa-Afa3), and the protein-free control that was conducted simultaneously. The columns (A-F) represent the following results, for each protein: B, the highest dilution showing complete RI; A, the next lower dilution relative to B; C, the next higher dilution relative to B ; D , the highest dilution showing clear partial RI; E,a higher dilution, not showing detectable RI; F,the control conducted simultaneously with A-E, using dilution buffer only. Each photograph shows a 520-pm hy 330-μm area of the appropriate frozen droplet. The dilution represented hy a photograph is shown helow it as a power of 2, e.g. at bottom left "-6" indicates the 2-6 dilution.
Ice Recrystallization Inhibition
PMID 8477839
DOI 10.1016/0014-5793(93)80090-H
Protein Name antifreeze analogue Afa3SB
Ice Recrystallization Inhibition Tab III Titration of recrystallization inhibition activities of free Afa peptides.
Ice Grow Rate
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa3SB
Tag SPA
Ice Grow Rate Tab.2 Antifreeze activity and helicity of synthetic antifreeze peptides.
Brief description
PMID: 2019569
DOI: 10.1016/S0021-9258(20)89451-4
1. Chimeric proteins containing antifreeze domains can inhibit ice recrystallization, and the IRI activity varies with the number of 11-amino-acid repeats in the antifreeze moiety.
2. The salt bridge and carboxyl-terminal arginine in the antifreeze protein seem to have a certain synergy effect on the IRI activity.
3. Proteins with two 11-amino-acid repeats lack significant IRI activity, while those with three, four, and five repeats show increasing inhibitory activities.
PMID: 8477839
DOI: 10.1016/0014-5793(93)80090-H
1. Antifreeze peptides require a minimum of three TA??A6? repeats (≥37 aa) to exhibit ice recrystallization inhibition activity; the two-repeat variant (Afa2) showed no activity even at high concentrations.
2. Increased peptide length enhances antifreeze potency; Afa4 (48 aa) and Afa5 (59 aa) showed lower MIC values (3–9 μg/ml) compared to shorter variants like Afa3 (12–40 μg/ml), indicating stronger recrystallization inhibition.
3. Engineered peptides lack C-terminal amidation, a key modification in natural antifreeze peptides, potentially explaining their reduced activity compared to native counterparts.

AFP011009013

Mutation Designed
Sequence
Ice Recrystallization Inhibition
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa4
Tag SPA
Ice Recrystallization Inhibition Fig.5 Recrystallization inhibition by chimeric proteins. The first row shows RI assays on dilutions of the Spa-X negative control. Theremaining rows each show dilutions of a particular chimeric protein (e.g. the row labeled Afa3 contains dilutions of Spa-Afa3), and the protein-free control that was conducted simultaneously. The columns (A-F) represent the following results, for each protein: B, the highest dilution showing complete RI; A, the next lower dilution relative to B; C, the next higher dilution relative to B ; D , the highest dilution showing clear partial RI; E,a higher dilution, not showing detectable RI; F,the control conducted simultaneously with A-E, using dilution buffer only. Each photograph shows a 520-pm hy 330-μm area of the appropriate frozen droplet. The dilution represented hy a photograph is shown helow it as a power of 2, e.g. at bottom left "-6" indicates the 2-6 dilution.
Ice Recrystallization Inhibition
PMID 8477839
DOI 10.1016/0014-5793(93)80090-H
Protein Name antifreeze analogue Afa4
Ice Recrystallization Inhibition Tab III Titration of recrystallization inhibition activities of free Afa peptides.
Brief description
PMID: 2019569
DOI: 10.1016/S0021-9258(20)89451-4
1. Chimeric proteins containing antifreeze domains can inhibit ice recrystallization, and the IRI activity varies with the number of 11-amino-acid repeats in the antifreeze moiety.
2. The salt bridge and carboxyl-terminal arginine in the antifreeze protein seem to have a certain synergy effect on the IRI activity.
3. Proteins with two 11-amino-acid repeats lack significant IRI activity, while those with three, four, and five repeats show increasing inhibitory activities.
PMID: 8477839
DOI: 10.1016/0014-5793(93)80090-H
1. Antifreeze peptides require a minimum of three TA??A6? repeats (≥37 aa) to exhibit ice recrystallization inhibition activity; the two-repeat variant (Afa2) showed no activity even at high concentrations.
2. Increased peptide length enhances antifreeze potency; Afa4 (48 aa) and Afa5 (59 aa) showed lower MIC values (3–9 μg/ml) compared to shorter variants like Afa3 (12–40 μg/ml), indicating stronger recrystallization inhibition.
3. Engineered peptides lack C-terminal amidation, a key modification in natural antifreeze peptides, potentially explaining their reduced activity compared to native counterparts.

AFP011009014

Mutation Designed
Sequence
Ice Recrystallization Inhibition
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa5
Tag SPA
Ice Recrystallization Inhibition Fig.5 Recrystallization inhibition by chimeric proteins. The first row shows RI assays on dilutions of the Spa-X negative control. Theremaining rows each show dilutions of a particular chimeric protein (e.g. the row labeled Afa3 contains dilutions of Spa-Afa3), and the protein-free control that was conducted simultaneously. The columns (A-F) represent the following results, for each protein: B, the highest dilution showing complete RI; A, the next lower dilution relative to B; C, the next higher dilution relative to B ; D , the highest dilution showing clear partial RI; E,a higher dilution, not showing detectable RI; F,the control conducted simultaneously with A-E, using dilution buffer only. Each photograph shows a 520-pm hy 330-μm area of the appropriate frozen droplet. The dilution represented hy a photograph is shown helow it as a power of 2, e.g. at bottom left "-6" indicates the 2-6 dilution.
Ice Recrystallization Inhibition
PMID 8477839
DOI 10.1016/0014-5793(93)80090-H
Protein Name antifreeze analogue Afa5
Ice Recrystallization Inhibition Tab III Titration of recrystallization inhibition activities of free Afa peptides.
Ice Recrystallization Inhibition
PMID 1932678
DOI 10.1007/BF00037141
Protein Name antifreeze analogue Afa5
Tag SPA
Ice Recrystallization Inhibition Fig.5 Ice recrystallization inhibition by Spa-Afa5 protein in transgenic tomato leaf extracts.
Brief description
PMID: 2019569
DOI: 10.1016/S0021-9258(20)89451-4
1. Chimeric proteins containing antifreeze domains can inhibit ice recrystallization, and the IRI activity varies with the number of 11-amino-acid repeats in the antifreeze moiety.
2. The salt bridge and carboxyl-terminal arginine in the antifreeze protein seem to have a certain synergy effect on the IRI activity.
3. Proteins with two 11-amino-acid repeats lack significant IRI activity, while those with three, four, and five repeats show increasing inhibitory activities.
PMID: 8477839
DOI: 10.1016/0014-5793(93)80090-H
1. Antifreeze peptides require a minimum of three TA??A6? repeats (≥37 aa) to exhibit ice recrystallization inhibition activity; the two-repeat variant (Afa2) showed no activity even at high concentrations.
2. Increased peptide length enhances antifreeze potency; Afa4 (48 aa) and Afa5 (59 aa) showed lower MIC values (3–9 μg/ml) compared to shorter variants like Afa3 (12–40 μg/ml), indicating stronger recrystallization inhibition.
3. Engineered peptides lack C-terminal amidation, a key modification in natural antifreeze peptides, potentially explaining their reduced activity compared to native counterparts.
PMID: 1932678
DOI: 10.1007/BF00037141
1. The Spa-Afa5 fusion protein (combining protein A and Afa5) was expressed and shown to be functional, exhibiting ice recrystallization inhibition (IRI) activity in plant extracts.
2. The expression of antifreeze proteins in plant tissue could inhibit ice recrystallization, potentially improving the post-harvest freeze/thaw quality of fruits and vegetables by reducing ice crystal damage.
3. This research provides the first evidence that functional antifreeze proteins can be produced in transgenic plants, opening avenues for enhancing cold tolerance and storage properties.

AFP011009015

Mutation Designed
Sequence
Ice Recrystallization Inhibition
PMID 2019569
DOI 10.1016/S0021-9258(20)89451-4
Protein Name antifreeze analogue Afa6
Tag SPA
Ice Recrystallization Inhibition Fig.5 Recrystallization inhibition by chimeric proteins. The first row shows RI assays on dilutions of the Spa-X negative control. Theremaining rows each show dilutions of a particular chimeric protein (e.g. the row labeled Afa3 contains dilutions of Spa-Afa3), and the protein-free control that was conducted simultaneously. The columns (A-F) represent the following results, for each protein: B, the highest dilution showing complete RI; A, the next lower dilution relative to B; C, the next higher dilution relative to B ; D , the highest dilution showing clear partial RI; E,a higher dilution, not showing detectable RI; F,the control conducted simultaneously with A-E, using dilution buffer only. Each photograph shows a 520-pm hy 330-μm area of the appropriate frozen droplet. The dilution represented hy a photograph is shown helow it as a power of 2, e.g. at bottom left "-6" indicates the 2-6 dilution.
Ice Recrystallization Inhibition
PMID 8477839
DOI 10.1016/0014-5793(93)80090-H
Protein Name antifreeze analogue Afa6
Ice Recrystallization Inhibition Tab III Titration of recrystallization inhibition activities of free Afa peptides.
Brief description
PMID: 2019569
DOI: 10.1016/S0021-9258(20)89451-4
1. Chimeric proteins containing antifreeze domains can inhibit ice recrystallization, and the IRI activity varies with the number of 11-amino-acid repeats in the antifreeze moiety.
2. The salt bridge and carboxyl-terminal arginine in the antifreeze protein seem to have a certain synergy effect on the IRI activity.
3. Proteins with two 11-amino-acid repeats lack significant IRI activity, while those with three, four, and five repeats show increasing inhibitory activities.
PMID: 8477839
DOI: 10.1016/0014-5793(93)80090-H
1. Antifreeze peptides require a minimum of three TA??A6? repeats (≥37 aa) to exhibit ice recrystallization inhibition activity; the two-repeat variant (Afa2) showed no activity even at high concentrations.
2. Increased peptide length enhances antifreeze potency; Afa4 (48 aa) and Afa5 (59 aa) showed lower MIC values (3–9 μg/ml) compared to shorter variants like Afa3 (12–40 μg/ml), indicating stronger recrystallization inhibition.
3. Engineered peptides lack C-terminal amidation, a key modification in natural antifreeze peptides, potentially explaining their reduced activity compared to native counterparts.

AFP011009016

Mutation L12T,T13L
Sequence
Thermal Hysteresis
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S04)
Thermal Hysteresis Tab.1 The winter flounder AFP (S00) and six analogs (S04-S40) were synthesized and assayed for antifreeze activity (7), which is defined here as the freezing point depression ofa 1 mM solution relative to that ofSOO. Circulardichroism data showed that all peptides were essentially 100% a-helical (7). Gaps have been placed so as to emphasize the 11-residue repeat sequences. In S00 the Asn (N), Asp (D), and Thr (T) residues, which form the polar face (see Fig. 1 C) ofthe a-helix, are in boldface. All ofthe mutations (underlined) are exchanges oftwo or three amino acids, except for S40, where the Leu residues are replaced by Ala. The bound peptide was energy-minimized as described in Fig. 2, and the computed hydrogen bonds were counted.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S04)
Thermal Hysteresis Fig.3 Dependence of antifreeze activity on AFP concentration. Assays were run in0.1 M ammonium bicarbonate buffer (pH 8.5). Activityisdefinedas the differencebetween the equilibrium melting pointof ice and the freezing point. Thepoor solubilityof SO4 prevented measurementsat higher concentrations.□,SOO; +,S04; ○,S11; ■,S22; x,S23; ◇,S4O; ▲,S12; ●,S21.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S04)
Thermal Hysteresis Tab.2 Relative activitiesof antifreeze peptidesos assessed by different Darameters
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S04)
Thermal Hysteresis Fig.3 Dependence of antifreeze activityon the square root of concentration, using data for Fig. 3.Solid lines are least squares plots of the data; broken lines in D illustrate a plot obtained assuming a two-step binding mechanism.
Ice Grow Rate
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S04)
Ice Grow Rate Fig.5 Ice crystal growth rates in dilute solutions of antifreeze peptides. A, rate of growth along thea axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperatureof ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of 4-6 rate measurements. □,SOO; +, S40; ●,S11; ○,S04; △,S22; ■,S23.
Brief description
PMID: 1489916
DOI: 10.1016/S0006-3495(92)81750-2
1. It is proposed that the antifreeze polypeptide from winter flounder inhibits ice crystal growth by hydrogen bonding of Thr, Asn and Asp side chains to the {2 0 2_ 1} hexagonal bipyramidal planes of ice in a specific pattern.
2. The binding mode is unidirectional, which increases the packing opportunities of antifreeze polypeptides on the ice surface and thus enhances the activity.
3. Ice crystal growth inhibition occurs through a two-step mechanism involving hydrogen bonding and hydrophobic interpeptide interactions. At low concentrations, it mainly depends on hydrogen bonding and ice crystals grow slowly; at high concentrations, hydrophobic interactions are enhanced and growth is inhibited.
PMID: 1629210
DOI: 10.1016/S0021-9258(19)49684-1
1. This study investigates HPLC-6, a 37-residue antifreeze polypeptide (AFP) from winter flounder (Pseudopleuronectes americanus), and its seven synthetic variants with rearranged neutral and polar amino acids.
2. A specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal antifreeze activity.
3. The development of antifreeze activity is at least a two-stage process. In dilute solution, AFP molecules bind to the ice surface in a specific manner to form hexagonal bipyramidal crystals. At a high enough concentration, the growth of bipyramidal crystals ceases, possibly due to cooperative interactions between helix molecules.

AFP011009017

Mutation N27A,A30N
Sequence
Thermal Hysteresis
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S11)
Thermal Hysteresis Tab.1 The winter flounder AFP (S00) and six analogs (S04-S40) were synthesized and assayed for antifreeze activity (7), which is defined here as the freezing point depression ofa 1 mM solution relative to that ofSOO. Circulardichroism data showed that all peptides were essentially 100% a-helical (7). Gaps have been placed so as to emphasize the 11-residue repeat sequences. In S00 the Asn (N), Asp (D), and Thr (T) residues, which form the polar face (see Fig. 1 C) ofthe a-helix, are in boldface. All ofthe mutations (underlined) are exchanges oftwo or three amino acids, except for S40, where the Leu residues are replaced by Ala. The bound peptide was energy-minimized as described in Fig. 2, and the computed hydrogen bonds were counted.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S11)
Thermal Hysteresis Fig.3 Dependence of antifreeze activity on AFP concentration. Assays were run in0.1 M ammonium bicarbonate buffer (pH 8.5). Activityisdefinedas the differencebetween the equilibrium melting pointof ice and the freezing point. Thepoor solubilityof SO4 prevented measurementsat higher concentrations.□,SOO; +,S04; ○,S11; ■,S22; x,S23; ◇,S4O; ▲,S12; ●,S21.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S11)
Thermal Hysteresis Tab.2 Relative activitiesof antifreeze peptidesos assessed by different Darameters
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S11)
Thermal Hysteresis Fig.3 Dependence of antifreeze activityon the square root of concentration, using data for Fig. 3.Solid lines are least squares plots of the data; broken lines in D illustrate a plot obtained assuming a two-step binding mechanism.
Ice Grow Rate
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S11)
Ice Grow Rate Fig.5 Ice crystal growth rates in dilute solutions of antifreeze peptides. A, rate of growth along thea axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperatureof ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of 4-6 rate measurements. □,SOO; +, S40; ●,S11; ○,S04; △,S22; ■,S23.
Brief description
PMID: 1489916
DOI: 10.1016/S0006-3495(92)81750-2
1. It is proposed that the antifreeze polypeptide from winter flounder inhibits ice crystal growth by hydrogen bonding of Thr, Asn and Asp side chains to the {2 0 2_ 1} hexagonal bipyramidal planes of ice in a specific pattern.
2. The binding mode is unidirectional, which increases the packing opportunities of antifreeze polypeptides on the ice surface and thus enhances the activity.
3. Ice crystal growth inhibition occurs through a two-step mechanism involving hydrogen bonding and hydrophobic interpeptide interactions. At low concentrations, it mainly depends on hydrogen bonding and ice crystals grow slowly; at high concentrations, hydrophobic interactions are enhanced and growth is inhibited.
PMID: 1629210
DOI: 10.1016/S0021-9258(19)49684-1
1. This study investigates HPLC-6, a 37-residue antifreeze polypeptide (AFP) from winter flounder (Pseudopleuronectes americanus), and its seven synthetic variants with rearranged neutral and polar amino acids.
2. A specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal antifreeze activity.
3. The development of antifreeze activity is at least a two-stage process. In dilute solution, AFP molecules bind to the ice surface in a specific manner to form hexagonal bipyramidal crystals. At a high enough concentration, the growth of bipyramidal crystals ceases, possibly due to cooperative interactions between helix molecules.
PMID: 9414201
DOI: 10.1016/S0006-3495(97)78315-2
1. The Asp, Asn, and Thr residues of AFP play important roles in ice binding. They can be divided into four ice-binding regions, and the spacing between these regions matches the ice lattice constant, enhancing the ice-binding ability.
2. The correct Thr-Asn distance and sequence are crucial for ice binding. When mutations change this distance and sequence, the antifreeze activity decreases.
3. The antifreeze activity of mutant S11 is 0.65 relative to the native AFP (set as 1.0). Its ice-binding properties show significant changes in the mutated region.

AFP011009018

Mutation T13N,N16T,N27A,A30N
Sequence
Thermal Hysteresis
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S23)
Thermal Hysteresis Tab.1 The winter flounder AFP (S00) and six analogs (S04-S40) were synthesized and assayed for antifreeze activity (7), which is defined here as the freezing point depression ofa 1 mM solution relative to that ofSOO. Circulardichroism data showed that all peptides were essentially 100% a-helical (7). Gaps have been placed so as to emphasize the 11-residue repeat sequences. In S00 the Asn (N), Asp (D), and Thr (T) residues, which form the polar face (see Fig. 1 C) ofthe a-helix, are in boldface. All ofthe mutations (underlined) are exchanges oftwo or three amino acids, except for S40, where the Leu residues are replaced by Ala. The bound peptide was energy-minimized as described in Fig. 2, and the computed hydrogen bonds were counted.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S23)
Thermal Hysteresis Fig.3 Dependence of antifreeze activity on AFP concentration. Assays were run in0.1 M ammonium bicarbonate buffer (pH 8.5). Activityisdefinedas the differencebetween the equilibrium melting pointof ice and the freezing point. Thepoor solubilityof SO4 prevented measurementsat higher concentrations.□,SOO; +,S04; ○,S11; ■,S22; x,S23; ◇,S4O; ▲,S12; ●,S21.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S23)
Thermal Hysteresis Tab.2 Relative activitiesof antifreeze peptidesos assessed by different Darameters
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S23)
Thermal Hysteresis Fig.3 Dependence of antifreeze activityon the square root of concentration, using data for Fig. 3.Solid lines are least squares plots of the data; broken lines in D illustrate a plot obtained assuming a two-step binding mechanism.
Ice Grow Rate
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S23)
Ice Grow Rate Fig.5 Ice crystal growth rates in dilute solutions of antifreeze peptides. A, rate of growth along thea axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperatureof ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of 4-6 rate measurements. □,SOO; +, S40; ●,S11; ○,S04; △,S22; ■,S23.
Brief description
PMID: 1489916
DOI: 10.1016/S0006-3495(92)81750-2
1. It is proposed that the antifreeze polypeptide from winter flounder inhibits ice crystal growth by hydrogen bonding of Thr, Asn and Asp side chains to the {2 0 2_ 1} hexagonal bipyramidal planes of ice in a specific pattern.
2. The binding mode is unidirectional, which increases the packing opportunities of antifreeze polypeptides on the ice surface and thus enhances the activity.
3. Ice crystal growth inhibition occurs through a two-step mechanism involving hydrogen bonding and hydrophobic interpeptide interactions. At low concentrations, it mainly depends on hydrogen bonding and ice crystals grow slowly; at high concentrations, hydrophobic interactions are enhanced and growth is inhibited.
PMID: 1629210
DOI: 10.1016/S0021-9258(19)49684-1
1. This study investigates HPLC-6, a 37-residue antifreeze polypeptide (AFP) from winter flounder (Pseudopleuronectes americanus), and its seven synthetic variants with rearranged neutral and polar amino acids.
2. A specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal antifreeze activity.
3. The development of antifreeze activity is at least a two-stage process. In dilute solution, AFP molecules bind to the ice surface in a specific manner to form hexagonal bipyramidal crystals. At a high enough concentration, the growth of bipyramidal crystals ceases, possibly due to cooperative interactions between helix molecules.
PMID: 9414201
DOI: 10.1016/S0006-3495(97)78315-2
1. The Asp, Asn, and Thr residues of AFP play important roles in ice binding. They can be divided into four ice-binding regions, and the spacing between these regions matches the ice lattice constant, enhancing the ice-binding ability.
2. The correct Thr-Asn distance and sequence are crucial for ice binding. When mutations change this distance and sequence, the antifreeze activity decreases.
3. Mutant S23 has a lower antifreeze activity of 0.17 relative to the native AFP. The key change comes from the interchange of Thr-13 and Asn-16.

AFP011009019

Mutation L12N,T13L,N16T,N27A,A30N
Sequence
Thermal Hysteresis
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S22)
Thermal Hysteresis Tab.1 The winter flounder AFP (S00) and six analogs (S04-S40) were synthesized and assayed for antifreeze activity (7), which is defined here as the freezing point depression ofa 1 mM solution relative to that ofSOO. Circulardichroism data showed that all peptides were essentially 100% a-helical (7). Gaps have been placed so as to emphasize the 11-residue repeat sequences. In S00 the Asn (N), Asp (D), and Thr (T) residues, which form the polar face (see Fig. 1 C) ofthe a-helix, are in boldface. All ofthe mutations (underlined) are exchanges oftwo or three amino acids, except for S40, where the Leu residues are replaced by Ala. The bound peptide was energy-minimized as described in Fig. 2, and the computed hydrogen bonds were counted.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S22)
Thermal Hysteresis Fig.3 Dependence of antifreeze activity on AFP concentration. Assays were run in0.1 M ammonium bicarbonate buffer (pH 8.5). Activityisdefinedas the differencebetween the equilibrium melting pointof ice and the freezing point. Thepoor solubilityof SO4 prevented measurementsat higher concentrations.□,SOO; +,S04; ○,S11; ■,S22; x,S23; ◇,S4O; ▲,S12; ●,S21.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S22)
Thermal Hysteresis Tab.2 Relative activitiesof antifreeze peptidesos assessed by different Darameters
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S22)
Thermal Hysteresis Fig.3 Dependence of antifreeze activityon the square root of concentration, using data for Fig. 3.Solid lines are least squares plots of the data; broken lines in D illustrate a plot obtained assuming a two-step binding mechanism.
Ice Grow Rate
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S22)
Ice Grow Rate Fig.5 Ice crystal growth rates in dilute solutions of antifreeze peptides. A, rate of growth along thea axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperatureof ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of 4-6 rate measurements. □,SOO; +, S40; ●,S11; ○,S04; △,S22; ■,S23.
Brief description
PMID: 1489916
DOI: 10.1016/S0006-3495(92)81750-2
1. It is proposed that the antifreeze polypeptide from winter flounder inhibits ice crystal growth by hydrogen bonding of Thr, Asn and Asp side chains to the {2 0 2_ 1} hexagonal bipyramidal planes of ice in a specific pattern.
2. The binding mode is unidirectional, which increases the packing opportunities of antifreeze polypeptides on the ice surface and thus enhances the activity.
3. Ice crystal growth inhibition occurs through a two-step mechanism involving hydrogen bonding and hydrophobic interpeptide interactions. At low concentrations, it mainly depends on hydrogen bonding and ice crystals grow slowly; at high concentrations, hydrophobic interactions are enhanced and growth is inhibited.
PMID: 1629210
DOI: 10.1016/S0021-9258(19)49684-1
1. This study investigates HPLC-6, a 37-residue antifreeze polypeptide (AFP) from winter flounder (Pseudopleuronectes americanus), and its seven synthetic variants with rearranged neutral and polar amino acids.
2. A specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal antifreeze activity.
3. The development of antifreeze activity is at least a two-stage process. In dilute solution, AFP molecules bind to the ice surface in a specific manner to form hexagonal bipyramidal crystals. At a high enough concentration, the growth of bipyramidal crystals ceases, possibly due to cooperative interactions between helix molecules.

AFP011009020

Mutation D5A,A6D,L12N,T13L,N27A,A30N
Sequence
Thermal Hysteresis
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S21)
Thermal Hysteresis Tab.1 The winter flounder AFP (S00) and six analogs (S04-S40) were synthesized and assayed for antifreeze activity (7), which is defined here as the freezing point depression ofa 1 mM solution relative to that ofSOO. Circulardichroism data showed that all peptides were essentially 100% a-helical (7). Gaps have been placed so as to emphasize the 11-residue repeat sequences. In S00 the Asn (N), Asp (D), and Thr (T) residues, which form the polar face (see Fig. 1 C) ofthe a-helix, are in boldface. All ofthe mutations (underlined) are exchanges oftwo or three amino acids, except for S40, where the Leu residues are replaced by Ala. The bound peptide was energy-minimized as described in Fig. 2, and the computed hydrogen bonds were counted.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S21)
Thermal Hysteresis Fig.3 Dependence of antifreeze activity on AFP concentration. Assays were run in0.1 M ammonium bicarbonate buffer (pH 8.5). Activityisdefinedas the differencebetween the equilibrium melting pointof ice and the freezing point. Thepoor solubilityof SO4 prevented measurementsat higher concentrations.□,SOO; +,S04; ○,S11; ■,S22; x,S23; ◇,S4O; ▲,S12; ●,S21.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S21)
Thermal Hysteresis Tab.2 Relative activitiesof antifreeze peptidesos assessed by different Darameters
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S21)
Thermal Hysteresis Fig.3 Dependence of antifreeze activityon the square root of concentration, using data for Fig. 3.Solid lines are least squares plots of the data; broken lines in D illustrate a plot obtained assuming a two-step binding mechanism.
Brief description
PMID: 1489916
DOI: 10.1016/S0006-3495(92)81750-2
1. It is proposed that the antifreeze polypeptide from winter flounder inhibits ice crystal growth by hydrogen bonding of Thr, Asn and Asp side chains to the {2 0 2_ 1} hexagonal bipyramidal planes of ice in a specific pattern.
2. The binding mode is unidirectional, which increases the packing opportunities of antifreeze polypeptides on the ice surface and thus enhances the activity.
3. Ice crystal growth inhibition occurs through a two-step mechanism involving hydrogen bonding and hydrophobic interpeptide interactions. At low concentrations, it mainly depends on hydrogen bonding and ice crystals grow slowly; at high concentrations, hydrophobic interactions are enhanced and growth is inhibited.
PMID: 1629210
DOI: 10.1016/S0021-9258(19)49684-1
1. This study investigates HPLC-6, a 37-residue antifreeze polypeptide (AFP) from winter flounder (Pseudopleuronectes americanus), and its seven synthetic variants with rearranged neutral and polar amino acids.
2. A specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal antifreeze activity.
3. The development of antifreeze activity is at least a two-stage process. In dilute solution, AFP molecules bind to the ice surface in a specific manner to form hexagonal bipyramidal crystals. At a high enough concentration, the growth of bipyramidal crystals ceases, possibly due to cooperative interactions between helix molecules.

AFP011009021

Mutation L12A,L23A
Sequence
Ice crystal morphology
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(ATAAN)
Ice crystal morphology Fig.4 Ice crystal morphologies of type I AFP mutants. Ice crystals were formed in the presence of approximately 1 mg/mL variant AFPs at 0.1 ℃ cooling.
Thermal Hysteresis
PMID 1489916
DOI 10.1016/S0006-3495(92)81750-2
Protein Name winter flounder AFP(S40)
Thermal Hysteresis Tab.1 The winter flounder AFP (S00) and six analogs (S04-S40) were synthesized and assayed for antifreeze activity (7), which is defined here as the freezing point depression ofa 1 mM solution relative to that ofSOO. Circulardichroism data showed that all peptides were essentially 100% a-helical (7). Gaps have been placed so as to emphasize the 11-residue repeat sequences. In S00 the Asn (N), Asp (D), and Thr (T) residues, which form the polar face (see Fig. 1 C) ofthe a-helix, are in boldface. All ofthe mutations (underlined) are exchanges oftwo or three amino acids, except for S40, where the Leu residues are replaced by Ala. The bound peptide was energy-minimized as described in Fig. 2, and the computed hydrogen bonds were counted.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S40)
Thermal Hysteresis Fig.3 Dependence of antifreeze activity on AFP concentration. Assays were run in0.1 M ammonium bicarbonate buffer (pH 8.5). Activityisdefinedas the differencebetween the equilibrium melting pointof ice and the freezing point. Thepoor solubilityof SO4 prevented measurementsat higher concentrations.□,SOO; +,S04; ○,S11; ■,S22; x,S23; ◇,S4O; ▲,S12; ●,S21.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S40)
Thermal Hysteresis Tab.2 Relative activitiesof antifreeze peptidesos assessed by different Darameters
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S40)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezing point.
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S40)
Thermal Hysteresis Tab.2 Antifreeze activity and helicity of synthetic antifreeze peptides
Thermal Hysteresis
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(ATAAN)
Thermal Hysteresis Fig.3.B Leu replacement variants: thermal hysteresis activities of ATAAT (●), ATAAN (O), and ATAAA (■) were compared over a range of concentrations. For reference, the activity profiles of their Leu-containing counterparts LTAAT (●), LTAAN (O), and LTAAA (□) are shown linked by dotted lines.
Ice Grow Rate
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S40)
Ice Grow Rate Fig.5 Ice crystal growth rates in dilute solutions of antifreeze peptides. A, rate of growth along thea axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperatureof ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of 4-6 rate measurements. □,SOO; +, S40; ●,S11; ○,S04; △,S22; ■,S23.
Ice Grow Rate
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S40)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze peptides. A, rate of growth along the a axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The transition point or threshold is that concentration below which ice crystal growth commences.
Brief description
PMID: 1489916
DOI: 10.1016/S0006-3495(92)81750-2
1. It is proposed that the antifreeze polypeptide from winter flounder inhibits ice crystal growth by hydrogen bonding of Thr, Asn and Asp side chains to the {2 0 2_ 1} hexagonal bipyramidal planes of ice in a specific pattern.
2. The binding mode is unidirectional, which increases the packing opportunities of antifreeze polypeptides on the ice surface and thus enhances the activity.
3. Ice crystal growth inhibition occurs through a two-step mechanism involving hydrogen bonding and hydrophobic interpeptide interactions. At low concentrations, it mainly depends on hydrogen bonding and ice crystals grow slowly; at high concentrations, hydrophobic interactions are enhanced and growth is inhibited.
PMID: 1629210
DOI: 10.1016/S0021-9258(19)49684-1
1. This study investigates HPLC-6, a 37-residue antifreeze polypeptide (AFP) from winter flounder (Pseudopleuronectes americanus), and its seven synthetic variants with rearranged neutral and polar amino acids.
2. A specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal antifreeze activity.
3. The development of antifreeze activity is at least a two-stage process. In dilute solution, AFP molecules bind to the ice surface in a specific manner to form hexagonal bipyramidal crystals. At a high enough concentration, the growth of bipyramidal crystals ceases, possibly due to cooperative interactions between helix molecules.
PMID: 8344925
DOI: 10.1016/S0021-9258(19)85434-0
1. Experimental results show that mutations replacing alanine with glutamine or leucine at certain positions significantly reduce thermal hysteresis (TH) activity, with S51 retaining 73% activity while S52 loses it completely.
2. Structural and ice-binding analyses suggest that these mutations alter protein stability and disrupt its interaction with ice, highlighting the importance of precise residue positioning in AFP function.
3. S40:Replaces Leu12 and Leu23 with Ala, retaining 67% activity (0.31°C at 1 mM). It maintains high helicity (~104%) and Tm (25.1°C), suggesting Leu residues contribute partially to activity but are not essential.
PMID: 10200162
DOI: 10.1021/bi982602p
1. Leu plays a crucial role in preventing the aggregation of alanine-rich helices at in vivo concentrations.
2. Asn may be more important for increasing peptide solubility than for binding to ice through traditional hydrogen bonding and/or steric complementarity.
3. The complete elimination of thermal hysteresis activity after replacing Asn with Gln (LTAAQ) having a larger side chain indicates that Asn may be in contact with the ice surface when type I antifreeze protein binds to the ice lattice.
4. The variant with the introduced ATAAT ice-binding motif (IBM) had higher activity than the wild type when solubility was maintained, but this might be due to the increased number of ice-binding repeats

AFP011009022

Mutation A20P
Sequence
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S12)
Thermal Hysteresis Fig.3 Dependence of antifreeze activity on AFP concentration. Assays were run in0.1 M ammonium bicarbonate buffer (pH 8.5). Activityisdefinedas the differencebetween the equilibrium melting pointof ice and the freezing point. Thepoor solubilityof SO4 prevented measurementsat higher concentrations.□,SOO; +,S04; ○,S11; ■,S22; x,S23; ◇,S4O; ▲,S12; ●,S21.
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S12)
Thermal Hysteresis Tab.2 Relative activitiesof antifreeze peptidesos assessed by different Darameters
Thermal Hysteresis
PMID 1629210
DOI 10.1016/S0021-9258(19)49684-1
Protein Name winter flounder AFP(S12)
Thermal Hysteresis Fig.3 Dependence of antifreeze activityon the square root of concentration, using data for Fig. 3.Solid lines are least squares plots of the data; broken lines in D illustrate a plot obtained assuming a two-step binding mechanism.
Brief description
PMID: 1629210
DOI: 10.1016/S0021-9258(19)49684-1
1. This study investigates HPLC-6, a 37-residue antifreeze polypeptide (AFP) from winter flounder (Pseudopleuronectes americanus), and its seven synthetic variants with rearranged neutral and polar amino acids.
2. A specific arrangement of both threonine and asparagine (or aspartic acid) residues is critical for maximal antifreeze activity.
3. The development of antifreeze activity is at least a two-stage process. In dilute solution, AFP molecules bind to the ice surface in a specific manner to form hexagonal bipyramidal crystals. At a high enough concentration, the growth of bipyramidal crystals ceases, possibly due to cooperative interactions between helix molecules.

AFP011009023

Mutation 37_38insG
Sequence
Thermal Hysteresis
PMID 8433967
DOI 10.1093/protein/6.1.19
Protein Name winter flounder HPLC-6'
Thermal Hysteresis Tab.1 AFP sequences with helicity and activity data.
Thermal Hysteresis
PMID 3769927
DOI 10.1111/j.1432-1033.1986.tb09966.x
Protein Name winter flounder AFP-6
Thermal Hysteresis Fig.3 The antifreeze activity of flounder pro-antifreezes plotted against concentration by mass ( A ) and against molar concentration ( B ) . Various amounts of proAFP-6, proAFP-8 and AFP-6 were dissolved in 0.01 M NH4HC03. Thermal hystereses of these materials were measured using a nanoliter osmometer. Each point, which is an average of four measurements, has a deviation of ±0.01℃.
Ice Binding Sites
PMID 8433967
DOI 10.1093/protein/6.1.19
Protein Name winter flounder HPLC-6'
IBS The ice-binding sites mainly involve Thr2, Thr13, Thr24 andThr35.
Brief description
PMID: 8433967
DOI: 10.1093/protein/6.1.19
1. The solution structure of the C-terminal region of the HPLC-6 precursor shows that the spacing between the side chains of Thr2, Thr13, Thr24 and Thr35 can match the repeat distance of oxygen atoms along the [0 1 1_ 2] direction in ice, which is beneficial for binding to the ice lattice.
PMID: 3769927
DOI: 10.1111/j.1432-1033.1986.tb09966.x
1. Two major pro-antifreezes corresponding to the precursors for AFP-6 and AFP-8 were isolated and characterized from winter flounder liver.
2. The pro-antifreezes were synthesized in the liver seasonally, starting in October and ceasing in March.
3. Both proAFP-6 and proAFP-8 showed antifreeze activity, but their activities were lower than those of the mature AFP.

AFP011009024

Mutation D1R,D5N,R37D
Sequence
Thermal Hysteresis
PMID 8433967
DOI 10.1093/protein/6.1.19
Protein Name winter flounder AFPV1
Thermal Hysteresis Tab.1 AFP sequences with helicity and activity data.
Brief description
PMID: 8433967
DOI: 10.1093/protein/6.1.19
1. The solution structure of the C-terminal region of the HPLC-6 precursor shows that the spacing between the side chains of Thr2, Thr13, Thr24 and Thr35 can match the repeat distance of oxygen atoms along the [0 1 1_ 2] direction in ice, which is beneficial for binding to the ice lattice.
2. Simulations of two engineered antifreeze protein variants (AFPV1 and AFPV2) showed that their solution structures and activities are consistent with the threonine-ice hydrogen bonding model.
3. AFPV1 had reduced activity due to partial unfolding of the α-helical structure, which increased the spacing between threonine side chains.

AFP011009025

Mutation A17K,K18A,A21E,E22A,37_38insG
Sequence
Thermal Hysteresis
PMID 8433967
DOI 10.1093/protein/6.1.19
Protein Name winter flounder AFPV2
Thermal Hysteresis Tab.1 AFP sequences with helicity and activity data.
Brief description
PMID: 8433967
DOI: 10.1093/protein/6.1.19
1. The solution structure of the C-terminal region of the HPLC-6 precursor shows that the spacing between the side chains of Thr2, Thr13, Thr24 and Thr35 can match the repeat distance of oxygen atoms along the [0 1 1_ 2] direction in ice, which is beneficial for binding to the ice lattice.
2. Simulations of two engineered antifreeze protein variants (AFPV1 and AFPV2) showed that their solution structures and activities are consistent with the threonine-ice hydrogen bonding model.
3. AFPV2, despite having threonine side chain spacing that matched the ice lattice, had low activity because the bulky side chains of Lys17 and Glu21 interfered with ice binding.

AFP011009026

Mutation E22A,A26E
Sequence
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S01)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S01)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Brief description
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. The COOH-terminus is relatively sensitive. Replacement of Arg37 by certain amino acids reduces helix content and antifreeze activity.
3. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
4. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.

AFP011009027

Mutation R37K
Sequence
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S14(2))
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S14(2))
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Brief description
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. Asp1 at the NH2 terminus does not contribute significantly to helix stability and antifreeze activity, but its deletion affects the ice crystal growth curve.
3. The COOH-terminus is relatively sensitive. Replacement of Arg37 by certain amino acids reduces helix content and antifreeze activity.
4. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
5. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.

AFP011009028

Mutation R37K,1del
Sequence
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S14(1))
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S14(1))
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Brief description
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. The COOH-terminus is relatively sensitive. Replacement of Arg37 by certain amino acids reduces helix content and antifreeze activity.
3. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
4. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.

AFP011009029

Mutation R37A
Sequence
Ice crystal morphology
PMID 20936690
DOI 10.1002/pro.516
Protein Name winter flounder rHPLC6-Ala37
Ice crystal morphology Fig.1 Activity of rHPLC6 and mutant constructs. (A) Ice crystal morphology of the four proteins in the thermal hysteretic gap. The identity of the protein is indicated below each photograph. The scale bar is the equivalent of 25 μm in length for all photographs.
Ice crystal morphology
PMID 20936690
DOI 10.1002/pro.516
Protein Name winter flounder rHPLC6-Ala37-NH2
PTM The recombinant protein rHPLC6-Ala37 was amidated at its C-terminal residue (Ala37) through the transamidase activity of carboxypeptidase-Y (CPD-Y).
Ice crystal morphology Fig.1 Activity of rHPLC6 and mutant constructs. (A) Ice crystal morphology of the four proteins in the thermal hysteretic gap. The identity of the protein is indicated below each photograph. The scale bar is the equivalent of 25 μm in length for all photographs.
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S33)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Thermal Hysteresis
PMID 20936690
DOI 10.1002/pro.516
Protein Name winter flounder rHPLC6-Ala37
Thermal Hysteresis Fig.1 Activity of rHPLC6 and mutant constructs. (B) Thermal hysteresis measurements. The activities of the constructs were measured using a nanoliter osmometer as described in the Material and Methods section. Synthetic HPLC6, open square; rHPLC6, open circle; rHPLC6-Ala37-NH2, open triangle; rHPLC6-Arg37, solid circle; rHPLC6-Ala37, solid triangle. The lines indicate the average trend for each of the proteins. Synthetic HPLC6 and rHPLC6, solid line; rHPLC6-Ala37-NH2, dotted and dashed line; rHPLC6-Arg37,dashed line; rHPLC6-Ala37, dotted line. The error bars represent the standard deviation of three independent measurements.
Thermal Hysteresis
PMID 20936690
DOI 10.1002/pro.516
Protein Name winter flounder rHPLC6-Ala37-NH2
PTM The recombinant protein rHPLC6-Ala37 was amidated at its C-terminal residue (Ala37) through the transamidase activity of carboxypeptidase-Y (CPD-Y).
Thermal Hysteresis Fig.1 Activity of rHPLC6 and mutant constructs. (B) Thermal hysteresis measurements. The activities of the constructs were measured using a nanoliter osmometer as described in the Material and Methods section. Synthetic HPLC6, open square; rHPLC6, open circle; rHPLC6-Ala37-NH2, open triangle; rHPLC6-Arg37, solid circle; rHPLC6-Ala37, solid triangle. The lines indicate the average trend for each of the proteins. Synthetic HPLC6 and rHPLC6, solid line; rHPLC6-Ala37-NH2, dotted and dashed line; rHPLC6-Arg37,dashed line; rHPLC6-Ala37, dotted line. The error bars represent the standard deviation of three independent measurements.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S33)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Brief description
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. The COOH-terminus is relatively sensitive. Replacement of Arg37 by certain amino acids reduces helix content and antifreeze activity.
3. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
4. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.
PMID: 20936690
DOI: 10.1002/pro.516
1. The nonamidated mutants had 35% lower thermal hysteresis (TH) activities compared to the amidated proteins. NMR and circular dichroism analysis showed that all proteins remained α-helical. Relaxation data indicated that the C-terminal residues of nonamidated mutants were more flexible due to the loss of the amide group, while the amidated Ala37 mutant had a rigid C-terminus and high TH activity.
2. The experiment proposes that the increase in the flexibility of AFP causes it to lose activity because its dynamic nature prevents it from strongly binding to the ice surface, and rigidity may be important for AFP to maintain close contact with the rigid ice surface.

AFP011009030

Mutation R37D
Sequence
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S34)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S34)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Brief description
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. Asp1 at the NH2 terminus does not contribute significantly to helix stability and antifreeze activity, but its deletion affects the ice crystal growth curve.
3. The COOH-terminus is relatively sensitive. Replacement of Arg37 by certain amino acids reduces helix content and antifreeze activity.
4. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
5. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.

AFP011009031

Mutation D1A
Sequence
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S35)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S35)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Brief description
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. Asp1 at the NH2 terminus does not contribute significantly to helix stability and antifreeze activity, but its deletion affects the ice crystal growth curve.
3. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
4. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.

AFP011009032

Mutation D1R
Sequence
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S36)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S36)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Brief description
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. Asp1 at the NH2 terminus does not contribute significantly to helix stability and antifreeze activity, but its deletion affects the ice crystal growth curve.
3. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
4. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.

AFP011009033

Mutation D1R,R37D
Sequence
Thermal Hysteresis
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S32)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezingpoint. Peptides having essentially identical activities (i.e. SOO, S33, 535, and S36; S14(1), S14(2), and S32) are represented with a singh line.
Ice Grow Rate
PMID 8344924
DOI 10.1016/S0021-9258(19)85433-9
Protein Name winter flounder AFP(S32)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze polypeptides. A , rate of growth along the a-axis; B , rate of growth along the c-axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The curves for S00 and S36 are nearly indistinguishable, showing sharp transitions at about 0.07 mM.
Brief description
PMID: 8344924
DOI: 10.1016/S0021-9258(19)85433-9
1. The i+4 ion pair (Lys18/Glu22) in the antifreeze protein helps to stabilize the α-helix, but is not absolutely essential for antifreeze activity.
2. Asp1 at the NH2 terminus does not contribute significantly to helix stability and antifreeze activity, but its deletion affects the ice crystal growth curve.
3. The COOH-terminus is relatively sensitive. Replacement of Arg37 by certain amino acids reduces helix content and antifreeze activity.
4. In general, factors that reduce the α-helix content usually also reduce antifreeze activity.
5. Asp5 is important for antifreeze activity. It may interact directly with the ice surface or stabilize the helix through charge-helix dipole interactions.

AFP011009034

Mutation T13S,T24S
Sequence
Ice crystal morphology
PMID 9398184
DOI 10.1021/bi970817d
Protein Name winter flounder LSAAN T13S,T24S
Ice crystal morphology Fig.4 Video microscopy of ice crystals in the presence of type I AFP and variants. Ice crystals were formed in the presence of 1 mg/mL peptide (or 16 mg/mL for LSAAN) in 0.1 M NH4HCO3 (pH 7.9) with an undercooling of 0.1 ℃. Still images at the start (0 min) and the end (10 min) of the undercooling trial are shown for the wild-type (Thr), LSAAN (Ser), and LVAAN (Val) protein.
Thermal Hysteresis
PMID 9398184
DOI 10.1021/bi970817d
Protein Name winter flounder LSAAN T13S,T24S
Thermal Hysteresis Fig.3 Antifreeze activity of type I AFP and its variants. Thermal hysteresis values for LTAAN (O), LVAAN (□), and LSAAN (●) are plotted as a function of concentration in 0.1 M NH4HCO3 (pH 7.9). Each data point represents the mean of at least three determinations. Standard deviations are shown as vertical bars.
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(TSST)
Thermal Hysteresis Fig.2.A Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Thermal Hysteresis
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(TSST)
Thermal Hysteresis "No hysteresis was observed with any of the serine-substituted analogues (TSST, SSSS, SSSS2KE) or the glycine-substituted derivative GGGG2KE."
Brief description
PMID: 9398184
DOI: 10.1021/bi970817d
1. When the two central threonines in the HPLC-6 isoform of type I antifreeze protein were mutated to serine, the antifreeze activity was almost completely lost.
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. TSST (Thr13 and Thr24→Ser) retains only 11% activity. It arrests growth at high concentrations but fails to induce needle-shaped crystals, with ice growing along both a- and c-axes. STTS (Thr2 and Thr35→Ser) retains 68% activity but also lacks the needle transition.
DOI: 10.1021/ja9801341
1. Threonine -OH groups are not required for antifreeze activity and hydrogen bonding may not play a crucial role in the ice - binding mechanism of antifreeze proteins.
2. The hydrophobic methyl groups in threonine and valine contribute significantly to antifreeze activity.
3. The native AFP and its mutants preferentially bind to the {2 0 2_ 1} ice plane, while the alanine mutant (AAAA2KE) binds to the {2 1_1_ 0} sculpin plane, highlighting differences in ice interaction. These findings suggest that hydrophobic interactions and specific amino acid substitutions influence ice plane selectivity and antifreeze activity.

AFP011009035

Mutation T13V,T24V
Sequence
Ice crystal morphology
PMID 9398184
DOI 10.1021/bi970817d
Protein Name winter flounder LVAAN T13V,T24V
Ice crystal morphology Fig.4 Video microscopy of ice crystals in the presence of type I AFP and variants. Ice crystals were formed in the presence of 1 mg/mL peptide (or 16 mg/mL for LSAAN) in 0.1 M NH4HCO3 (pH 7.9) with an undercooling of 0.1 ℃. Still images at the start (0 min) and the end (10 min) of the undercooling trial are shown for the wild-type (Thr), LSAAN (Ser), and LVAAN (Val) protein.
Thermal Hysteresis
PMID 9398184
DOI 10.1021/bi970817d
Protein Name winter flounder LVAAN T13V,T24V
Thermal Hysteresis Fig.3 Antifreeze activity of type I AFP and its variants. Thermal hysteresis values for LTAAN (O), LVAAN (□), and LSAAN (●) are plotted as a function of concentration in 0.1 M NH4HCO3 (pH 7.9). Each data point represents the mean of at least three determinations. Standard deviations are shown as vertical bars.
Thermal Hysteresis
PMID 22853917
DOI 10.1016/j.bpj.2012.06.013
Protein Name winter flounder AFP(VAVA)
Thermal Hysteresis Fig.1 Freezing point hysteresis in 100 mM NH4HCO3 buffer.VAVA (Yellow open diamonds).
Brief description
PMID: 9398184
DOI: 10.1021/bi970817d
1. When the two central threonines in the HPLC-6 isoform of type I antifreeze protein were mutated to valine, only a minor loss of antifreeze activity was observed.
PMID: 22853917
DOI: 10.1016/j.bpj.2012.06.013
1. The pseudo-wild-type TATW and its three mutants TLTW, SASW, VAVW of winter flounder antifreeze peptide (wf-AFP1) were synthesized, and their thermal hysteresis activities were determined by freezing point hysteresis experiments. The activity ranking was found to be TATA>TATW>VAVA>VAVW>WLTW>SASW.
2. Circular dichroism (CD) experiments SASW showed that although had a high helix content at room temperature, its activity was low. The helix content of TATW, TLTW, and VAVA increased at and their activities were higher than that of SASW, indicating that a large helix content does not guarantee activity.
3. Short-range ice binding and long-range solvent perturbation are two mechanisms related to the activity of antifreeze proteins and glycoproteins.The results showed that the short-range model can explain the activity of mutants, while the long-range model is a necessary condition for activity, as the most active peptides all have an extended dynamical hydration shell. It seems that antifreeze proteins and glycoproteins have evolved different solutions to the antifreeze problem.

AFP011009036

Mutation T13V,T24V,A33W
Sequence
Thermal Hysteresis
PMID 22853917
DOI 10.1016/j.bpj.2012.06.013
Protein Name winter flounder AFP(VAVW)
Thermal Hysteresis Fig.1 Freezing point hysteresis in 100 mM NH4HCO3 buffer.VAVW (Yellow filled diamonds).
Brief description
PMID: 22853917
DOI: 10.1016/j.bpj.2012.06.013
1. The pseudo-wild-type TATW and its three mutants TLTW, SASW, VAVW of winter flounder antifreeze peptide (wf-AFP1) were synthesized, and their thermal hysteresis activities were determined by freezing point hysteresis experiments. The activity ranking was found to be TATA>TATW>VAVA>VAVW>WLTW>SASW.
2. Circular dichroism (CD) experiments SASW showed that although had a high helix content at room temperature, its activity was low. The helix content of TATW, TLTW, and VAVA increased at and their activities were higher than that of SASW, indicating that a large helix content does not guarantee activity.
3. Short-range ice binding and long-range solvent perturbation are two mechanisms related to the activity of antifreeze proteins and glycoproteins.The results showed that the short-range model can explain the activity of mutants, while the long-range model is a necessary condition for activity, as the most active peptides all have an extended dynamical hydration shell. It seems that antifreeze proteins and glycoproteins have evolved different solutions to the antifreeze problem.

AFP011009037

Mutation A7Q,A14Q,A25Q,A32Q
Sequence
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S50)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezing point.
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S50)
Thermal Hysteresis Tab.2 Antifreeze activity and helicity of synthetic antifreeze peptides
Ice Grow Rate
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S50)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze peptides. A, rate of growth along the a axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The transition point or threshold is that concentration below which ice crystal growth commences.
Brief description
PMID: 8344925
DOI: 10.1016/S0021-9258(19)85434-0
1. Experimental results show that mutations replacing alanine with glutamine or leucine at certain positions significantly reduce thermal hysteresis (TH) activity, with S51 retaining 73% activity while S52 loses it completely.
2. Structural and ice-binding analyses suggest that these mutations alter protein stability and disrupt its interaction with ice, highlighting the importance of precise residue positioning in AFP function.
3. S50: Contains Gln substitutions at positions 7, 14, 25, and 32. It shows only 11% activity (0.05°C at 1 mM) with no sharp growth-arrest transition, even at high concentrations (>3.0 mM).

AFP011009038

Mutation A8Q,A15Q,A26Q,A33Q
Sequence
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S51)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezing point.
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S51)
Thermal Hysteresis Tab.2 Antifreeze activity and helicity of synthetic antifreeze peptides
Ice Grow Rate
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S51)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze peptides. A, rate of growth along the a axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The transition point or threshold is that concentration below which ice crystal growth commences.
Brief description
PMID: 8344925
DOI: 10.1016/S0021-9258(19)85434-0
1. Experimental results show that mutations replacing alanine with glutamine or leucine at certain positions significantly reduce thermal hysteresis (TH) activity, with S51 retaining 73% activity while S52 loses it completely.
2. Structural and ice-binding analyses suggest that these mutations alter protein stability and disrupt its interaction with ice, highlighting the importance of precise residue positioning in AFP function.
3. S51: Has Gln substitutions at positions 8, 15, 26, and 33. It retains 73% activity (0.34°C at 1 mM) with a functional concentration threshold. Despite reduced helix stability (90% helicity, Tm = 18.5°C), its non-ice-binding face modifications are well-tolerated, indicating bulk hydrophobicity of this face is not critical.

AFP011009039

Mutation A8Q,A17Q,A26Q,A28Q
Sequence
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S52)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezing point.
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S52)
Thermal Hysteresis Tab.2 Antifreeze activity and helicity of synthetic antifreeze peptides
Brief description
PMID: 8344925
DOI: 10.1016/S0021-9258(19)85434-0
1. Experimental results show that mutations replacing alanine with glutamine or leucine at certain positions significantly reduce thermal hysteresis (TH) activity, with S51 retaining 73% activity while S52 loses it completely.
2. Structural and ice-binding analyses suggest that these mutations alter protein stability and disrupt its interaction with ice, highlighting the importance of precise residue positioning in AFP function.
3. S52: Carries Gln substitutions at positions 8, 17, 26, and 28. It is completely inactive (0°C) due to steric hindrance from the Gln at position 17, which blocks cooperative packing of AFP molecules on the ice surface.

AFP011009040

Mutation A8L,L12A,A17L,L23A
Sequence
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S41)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezing point.
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S41)
Thermal Hysteresis Tab.2 Antifreeze activity and helicity of synthetic antifreeze peptides
Brief description
PMID: 8344925
DOI: 10.1016/S0021-9258(19)85434-0
1. Experimental results show that mutations replacing alanine with glutamine or leucine at certain positions significantly reduce thermal hysteresis (TH) activity, with S51 retaining 73% activity while S52 loses it completely.
2. Structural and ice-binding analyses suggest that these mutations alter protein stability and disrupt its interaction with ice, highlighting the importance of precise residue positioning in AFP function.
3. S41:S41 has Leu at positions 8 and 17. It is completely inactive (0°C) despite full helicity.

AFP011009041

Mutation L12A,A17L,L23A
Sequence
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S42)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezing point.
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S42)
Thermal Hysteresis Tab.2 Antifreeze activity and helicity of synthetic antifreeze peptides
Brief description
PMID: 8344925
DOI: 10.1016/S0021-9258(19)85434-0
1. Experimental results show that mutations replacing alanine with glutamine or leucine at certain positions significantly reduce thermal hysteresis (TH) activity, with S51 retaining 73% activity while S52 loses it completely.
2. Structural and ice-binding analyses suggest that these mutations alter protein stability and disrupt its interaction with ice, highlighting the importance of precise residue positioning in AFP function.
3. S42 has Leu only at position 17. It is completely inactive (0°C) despite full helicity.

AFP011009042

Mutation A8L,L12A,L23A
Sequence
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S43)
Thermal Hysteresis Fig.1 Dependence of antifreeze activity on AFP concentration. Assays wererun in0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and thefreezing point.
Thermal Hysteresis
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S43)
Thermal Hysteresis Tab.2 Antifreeze activity and helicity of synthetic antifreeze peptides
Ice Grow Rate
PMID 8344925
DOI 10.1016/S0021-9258(19)85434-0
Protein Name winter flounder AFP(S43)
Ice Grow Rate Fig.2 Ice crystal growth rates indilute solutions of antifreeze peptides. A, rate of growth along the a axis; B, rate of growth along the c axis. Solutions were cooled 0.1 ℃ below the equilibrium melting temperature of ice, and crystal size as a function of time was recorded on videotape. Each point above 0 μm/min represents the average of four to six rate measurements. The transition point or threshold is that concentration below which ice crystal growth commences.
Brief description
PMID: 8344925
DOI: 10.1016/S0021-9258(19)85434-0
1. Experimental results show that mutations replacing alanine with glutamine or leucine at certain positions significantly reduce thermal hysteresis (TH) activity, with S51 retaining 73% activity while S52 loses it completely.
2. Structural and ice-binding analyses suggest that these mutations alter protein stability and disrupt its interaction with ice, highlighting the importance of precise residue positioning in AFP function.
3. S43:Substitutes Ala8 with Leu, retaining 63% activity (0.29°C at 1 mM). This indicates position 8 tolerates bulky groups without disrupting cooperative packing, unlike position 17.

AFP011009043

Mutation T13S
Sequence
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(TSTT)
Thermal Hysteresis Fig.2.A Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. TSTT (Thr13→Ser), TTST (Thr24→Ser), and TTTS (Thr35→Ser) retain 84%, 76%, and 91% of the native activity, respectively. They maintain α-helicity (~100%) and can still arrest ice crystal growth, with ice morphology similar to TTTT (forming hexagonal bipyramids and needle-shaped crystals at the freezing point).

AFP011009044

Mutation T24S
Sequence
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(TTST)
Thermal Hysteresis Fig.2.A Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. TSTT (Thr13→Ser), TTST (Thr24→Ser), and TTTS (Thr35→Ser) retain 84%, 76%, and 91% of the native activity, respectively. They maintain α-helicity (~100%) and can still arrest ice crystal growth, with ice morphology similar to TTTT (forming hexagonal bipyramids and needle-shaped crystals at the freezing point).

AFP011009045

Mutation T35S
Sequence
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(TTTS)
Thermal Hysteresis Fig.2.A Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. TSTT (Thr13→Ser), TTST (Thr24→Ser), and TTTS (Thr35→Ser) retain 84%, 76%, and 91% of the native activity, respectively. They maintain α-helicity (~100%) and can still arrest ice crystal growth, with ice morphology similar to TTTT (forming hexagonal bipyramids and needle-shaped crystals at the freezing point).

AFP011009046

Mutation T2S,T25S
Sequence
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(STTS)
Thermal Hysteresis Fig.2.A Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. TSST (Thr13 and Thr24→Ser) retains only 11% activity. It arrests growth at high concentrations but fails to induce needle-shaped crystals, with ice growing along both a- and c-axes. STTS (Thr2 and Thr35→Ser) retains 68% activity but also lacks the needle transition.

AFP011009047

Mutation T2S,T24S,T35S
Sequence
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(STSS)
Thermal Hysteresis Fig.2.A Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. STSS (three Thr→Ser) and SSSS (all four Thr→Ser) are completely inactive, unable to arrest ice growth.

AFP011009048

Mutation T2S,T13S,T24S,T35S
Sequence
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(SSSS)
Thermal Hysteresis Fig.2.A Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Thermal Hysteresis
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(SSSS)
Thermal Hysteresis "No hysteresis was observed with any of the serine-substituted analogues (TSST, SSSS, SSSS2KE) or the glycine-substituted derivative GGGG2KE."
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. STSS (three Thr→Ser) and SSSS (all four Thr→Ser) are completely inactive, unable to arrest ice growth.
DOI: 10.1021/ja9801341
1. Threonine -OH groups are not required for antifreeze activity and hydrogen bonding may not play a crucial role in the ice-binding mechanism of antifreeze proteins.
2. The hydrophobic methyl groups in threonine and valine contribute significantly to antifreeze activity.
3. The native AFP and its mutants preferentially bind to the {2 0 2_ 1} ice plane, while the alanine mutant (AAAA2KE) binds to the {2 1_1_ 0} sculpin plane, highlighting differences in ice interaction. These findings suggest that hydrophobic interactions and specific amino acid substitutions influence ice plane selectivity and antifreeze activity.

AFP011009049

Mutation T13t
Sequence
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(TtTT)
Thermal Hysteresis Fig.2.B Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. TτTT retains 96% activity, with ice-binding and morphology similar to TTTT.

AFP011009050

Mutation T2t/T13t/T24t/T35t
Sequence
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(tttt)
Thermal Hysteresis Fig.2.B Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. ττττ (all four Thr→allo-Thr) retains ~30% activity. It completely arrests ice growth at high concentrations but does not induce needle-shaped crystals, with ice growing along both axes.

AFP011009051

Mutation T2V,A7K,A10E,T13V,T24V,A29K,A33E,T35V
Sequence
Ice crystal morphology
PMID 9688560
DOI 10.1016/s0014-5793(98)00652-8
Protein Name winter flounder AFP(VVVV2KE)
Ice crystal morphology Fig.1 Bipyramidal ice crystal grown from an unfaceted seed crystal in a 9.8 mg/ml solution of VVVV2KE in water.
Ice crystal morphology
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(VVVV2KE)
Ice crystal morphology Fig.3 Still images of ice crystals grown from solutions of (a) TTTT (~5mg mL-1), (b) TTTT2KE (4 mg mL-1), (c) VVVV2KE34 (10 mg mL-1), and (d) AAAA2KE (5 mg mL-1). Video microscopy of ice crystals in the absence and presence of antifreeze proteins: (e) GGGG2KE (10 mg mL-1), (f) TTTT2KE (4 mg mL-1), (g) VVVV2KE (10 mg mL-1). Still images are taken at regular intervals over a period of 1 min.
Thermal Hysteresis
PMID 9857006
DOI 10.1074/jbc.273.52.34806
Protein Name winter flounder AFP(VVVV2KE)
Thermal Hysteresis Fig.2.B Dependence of antifreeze activity on AFP concentration. Assays were run in 0.1 M ammonium bicarbonate buffer (pH 8.5). Activity is defined as the difference between the equilibrium melting point of ice and the freezing point. Panel A, Ser mutants: TTTT (■), TSTT (□) ,TTST (●), TTTS (○), STTS (+), TSST (x), STSS (▲), SSSS (△). Panel B, allo-Thr and Val mutants: TTTT(■), TtTT (□), tttt (●), VVVV2KE (○).
Thermal Hysteresis
PMID 9688560
DOI 10.1016/s0014-5793(98)00652-8
Protein Name winter flounder AFP(VVVV2KE)
Thermal Hysteresis "This hysteresis behavior for VVVV2KE (the separation of the ice growth temperature and the melting temperature) is concentration dependent, and compared with the native protein TTTT is about half as active at a concentration of 10 mg/ml."
Thermal Hysteresis
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(VVVV2KE)
Thermal Hysteresis Fig.1 Measured thermal hysteresis as a function of concentration (a) 0 to 33 mg mL-1; (b) 0 to 6 mg mL-1 for solutions of TTTT (squares), TTTT2KE (diamonds), VVVV2KE (disks), and AAAA2KE (triangles). TTTT data summarized from Duman and DeVries15 is denoted by the solid line. The thin line near zero temperature is the (thermodynamic) colligative depression of the equilibrium freezing point at these concentrations.
Ice Hemisphere Etching
PMID 9688560
DOI 10.1016/s0014-5793(98)00652-8
Protein Name winter flounder AFP(VVVV2KE)
Ice Hemisphere Etching Fig.2 Top view of oriented, single crystal ice hemisphere grown from a 0.10 mg/ml solution of VVVV2KE in water. The etch patterns are oriented on the {2 0 2_ 1} plane of ice 1h.
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(VVVV2KE)
Ice Hemisphere Etching Fig.4 Top view of oriented single-crystal ice hemispheres grown from 0.03 mg mL-1 solutions of (a) TTTT,19 (b) TTTT2KE, and (c) VVVV2KE34 for comparison (d) AAAA2KE and (e) GGGG2KE. The ice 1h c-axis points vertically up the page. Lighting is provided by two lamps above the hemispheres, seen clearly in (e) the etch-free pattern. Side views of (f) the VVVV2KE hemisphere in panel (c), where straight white lines have been added above the crystal to highlight the distortion of the hemisphere into planes due to the presence of peptide, and (g) the AAAA2KE hemisphere in panel (d).
Ice plane
PMID 9688560
DOI 10.1016/s0014-5793(98)00652-8
Protein Name winter flounder AFP(VVVV2KE)
Ice plane Type I antifreeze proteins of winter flounder (including the native protein TTTT and the mutant VVVV2KE) accumulate on the {2 0 2_ 1} plane of ice.
Ice plane
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(VVVV2KE)
Ice plane The Ice-plane includes the {2 0 2_ 1} binding plane.
Brief description
PMID: 9857006
DOI: 10.1074/jbc.273.52.34806
1. The methyl and hydroxyl groups of threonine, particularly those of the central two threonine residues, are crucial for antifreeze activity.
2. Substituting threonine with serine leads to varying degrees of loss of antifreeze activity, and the replacement of the methyl group has a greater impact on antifreeze activity.
3. VVVV2KE retains 30% activity. Ice crystal growth is very slow even at high concentrations, with no abrupt transition to needles; instead, crystals enlarge along both a- and c-axes.
PMID: 9688560
DOI: 10.1016/s0014-5793(98)00652-8
1. This study investigates the role of threonine residues in the antifreeze activity of a type I antifreeze protein from winter flounder.
2. The valine mutant (VVVV2KE) retained antifreeze activity similar to that of the native antifreeze protein, while the serine mutant (SSSS2KE) and glycine mutant (GGGG2KE) did not show antifreeze activity. This indicates that the threonine hydroxyl groups are not crucial for the accumulation of the native antifreeze protein at the ice/water interface and the inhibition of ice growth.
3. Through the mutation study of the four threonine residues of the type I antifreeze protein from winter flounder, it was found that hydrogen bonding is not necessary for the strong antifreeze action of antifreeze proteins.
DOI: 10.1021/ja9801341
1. Threonine -OH groups are not required for antifreeze activity and hydrogen bonding may not play a crucial role in the ice-binding mechanism of antifreeze proteins.
2. The hydrophobic methyl groups in threonine and valine contribute significantly to antifreeze activity.
3. The native AFP and its mutants preferentially bind to the {2 0 2_ 1} ice plane, while the alanine mutant (AAAA2KE) binds to the {2 1_1_ 0} sculpin plane, highlighting differences in ice interaction. These findings suggest that hydrophobic interactions and specific amino acid substitutions influence ice plane selectivity and antifreeze activity.
PMID: 11856360
DOI: 10.1046/j.1432-1033.2002.02766.x
1. The antifreeze activity of the VVVV2KE mutant is similar to that of the wild - type HPLC6 (TTTT), indicating that the mutation of Thr to Val and the introduction of additional salt bridges do not affect the antifreeze activity.
2. Experimental data show that hydrogen bonds involving the hydroxyl groups of the four Thr residues are not the primary reason for the interaction of TTTT with the ice/water interfacial region.

AFP011009052

Mutation T2S,T13S,T24S,T35S,A7K,A11K,A29K,A33E
Sequence
Ice crystal morphology
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(BBBB2KE)
Ice crystal morphology Fig.2 Video microscopy images of ice crystal growth in the presence of (a) BBBB2KE, (b) IIII2KE, (c) TTTTAL2KE and (d) VVVVAL2KE. All concentrations are in the range 6-7 mM.
Thermal Hysteresis
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(SSSS2KE)
Thermal Hysteresis "No hysteresis was observed with any of the serine-substituted analogues (TSST, SSSS, SSSS2KE) or the glycine-substituted derivative GGGG2KE."
Thermal Hysteresis
PMID 9688560
DOI 10.1016/s0014-5793(98)00652-8
Protein Name winter flounder AFP(SSSS2KE)
Thermal Hysteresis "Similar experiments were carried out with SSSS2KE and GGGG2KE, but neither peptide exhibited any hysteresis behavior."
Thermal Hysteresis
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(BBBB2KE)
Thermal Hysteresis Fig.1 Thermal hysteresis as a function of concentration for unbuffered solution of BBBB2KE (filled circles). For comparison, published hysteresis date for the native protein TTTT (open circles) [7] TTTT2KE (diamonds) and hydrophobic analogues VVVV2KE (squares) and AAAA2KE (triangles) [21] are also included.
Brief description
DOI: 10.1021/ja9801341
1. Threonine -OH groups are not required for antifreeze activity and hydrogen bonding may not play a crucial role in the ice-binding mechanism of antifreeze proteins.
2. The hydrophobic methyl groups in threonine and valine contribute significantly to antifreeze activity.
3. The native AFP and its mutants preferentially bind to the {2 0 2_ 1} ice plane, while the alanine mutant (AAAA2KE) binds to the {2 1_1_ 0} sculpin plane, highlighting differences in ice interaction. These findings suggest that hydrophobic interactions and specific amino acid substitutions influence ice plane selectivity and antifreeze activity.
PMID: 9688560
DOI: 10.1016/s0014-5793(98)00652-8
1. This study investigates the role of threonine residues in the antifreeze activity of a type I antifreeze protein from winter flounder.
2. The valine mutant (VVVV2KE) retained antifreeze activity similar to that of the native antifreeze protein, while the serine mutant (SSSS2KE) and glycine mutant (GGGG2KE) did not show antifreeze activity. This indicates that the threonine hydroxyl groups are not crucial for the accumulation of the native antifreeze protein at the ice/water interface and the inhibition of ice growth.
3. Through the mutation study of the four threonine residues of the type I antifreeze protein from winter flounder, it was found that hydrogen bonding is not necessary for the strong antifreeze action of antifreeze proteins.
PMID: 11240143
DOI: 10.1016/s0014-5793(01)02213-x
1. The γ-methyl group of threonine alone is not sufficient to confer ice-growth inhibition properties. The presence of the OH group and the γ-methyl in TTTT, or an additional methyl group like in VVVV2KE, confers significantly higher thermal hysteresis.
2. The IIII2KE with isoleucine replacing threonine can modify the ice crystal shape but shows no thermal hysteresis, indicating that replacing the hydroxyl group of threonine in TTTT with an ethyl group removes the ability to inhibit ice growth.
3. TTTTAL2KE and VVVVAL2KE with mutations in aspartic acid (Asp) and asparagine (Asn) show no thermal hysteresis, confirming the involvement of these Asx residues in the ice-growth inhibition mechanism.

AFP011009053

Mutation T2G,A7K,A10E,T13G,T24G,A29K,A33E,T35G
Sequence
Thermal Hysteresis
PMID 9688560
DOI 10.1016/s0014-5793(98)00652-8
Protein Name winter flounder AFP(GGGG2KE)
Thermal Hysteresis "Similar experiments were carried out with SSSS2KE and GGGG2KE, but neither peptide exhibited any hysteresis behavior."
Thermal Hysteresis
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(GGGG2KE)
Thermal Hysteresis "No hysteresis was observed with any of the serine-substituted analogues (TSST, SSSS, SSSS2KE) or the glycine-substituted derivative GGGG2KE."
Brief description
PMID: 9688560
DOI: 10.1016/s0014-5793(98)00652-8
1. This study investigates the role of threonine residues in the antifreeze activity of a type I antifreeze protein from winter flounder.
2. The valine mutant (VVVV2KE) retained antifreeze activity similar to that of the native antifreeze protein, while the serine mutant (SSSS2KE) and glycine mutant (GGGG2KE) did not show antifreeze activity. This indicates that the threonine hydroxyl groups are not crucial for the accumulation of the native antifreeze protein at the ice/water interface and the inhibition of ice growth.
3. Through the mutation study of the four threonine residues of the type I antifreeze protein from winter flounder, it was found that hydrogen bonding is not necessary for the strong antifreeze action of antifreeze proteins.
DOI: 10.1021/ja9801341
1. Threonine -OH groups are not required for antifreeze activity and hydrogen bonding may not play a crucial role in the ice-binding mechanism of antifreeze proteins.
2. The hydrophobic methyl groups in threonine and valine contribute significantly to antifreeze activity.
3. The native AFP and its mutants preferentially bind to the {2 0 2_ 1} ice plane, while the alanine mutant (AAAA2KE) binds to the {2 1_1_ 0} sculpin plane, highlighting differences in ice interaction. These findings suggest that hydrophobic interactions and specific amino acid substitutions influence ice plane selectivity and antifreeze activity.

AFP011009054

Mutation T2A,T13A,T24A,T35A,A7K,A11K,A29K,A33E
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(AAAA2KE)
Ice crystal morphology Fig.3 Still images of ice crystals grown from solutions of (a) TTTT (~5mg mL-1), (b) TTTT2KE (4 mg mL-1), (c) VVVV2KE34 (10 mg mL-1), and (d) AAAA2KE (5 mg mL-1). Video microscopy of ice crystals in the absence and presence of antifreeze proteins: (e) GGGG2KE (10 mg mL-1), (f) TTTT2KE (4 mg mL-1), (g) VVVV2KE (10 mg mL-1). Still images are taken at regular intervals over a period of 1 min.
Thermal Hysteresis
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(AAAA2KE)
Thermal Hysteresis Fig.1 Measured thermal hysteresis as a function of concentration (a) 0 to 33 mg mL-1; (b) 0 to 6 mg mL-1 for solutions of TTTT (squares), TTTT2KE (diamonds), VVVV2KE (disks), and AAAA2KE (triangles). TTTT data summarized from Duman and DeVries15 is denoted by the solid line. The thin line near zero temperature is the (thermodynamic) colligative depression of the equilibrium freezing point at these concentrations.
Thermal Hysteresis
PMID 28956610
DOI 10.1021/acs.jpcb.7b06619
Protein Name winter flounder AFP(AAAA2kE)
Thermal Hysteresis Fig.3 Thermal hysteresis temperatures of AAAA2kE solution as functions of the AFP concentration with (-) and without (---) including the adsorption orientation. The experimental data2 are shown as ■.
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(AAAA2KE)
Ice Hemisphere Etching Fig.4 Top view of oriented single-crystal ice hemispheres grown from 0.03 mg mL-1 solutions of (a) TTTT,19 (b) TTTT2KE, and (c) VVVV2KE34 for comparison (d) AAAA2KE and (e) GGGG2KE. The ice 1h c-axis points vertically up the page. Lighting is provided by two lamps above the hemispheres, seen clearly in (e) the etch-free pattern. Side views of (f) the VVVV2KE hemisphere in panel (c), where straight white lines have been added above the crystal to highlight the distortion of the hemisphere into planes due to the presence of peptide, and (g) the AAAA2KE hemisphere in panel (d).
Ice plane
PMID N/A
DOI 10.1021/ja9801341
Protein Name winter flounder AFP(AAAA2KE)
Ice plane The Ice-plane includes the {2 1_ 1_ 0} ice surface.
Brief description
DOI: 10.1021/ja9801341
1. Threonine -OH groups are not required for antifreeze activity and hydrogen bonding may not play a crucial role in the ice-binding mechanism of antifreeze proteins.
2. The hydrophobic methyl groups in threonine and valine contribute significantly to antifreeze activity.
3. The native AFP and its mutants preferentially bind to the {2 0 2_ 1} ice plane, while the alanine mutant (AAAA2KE) binds to the {2 1_1_ 0} sculpin plane, highlighting differences in ice interaction. These findings suggest that hydrophobic interactions and specific amino acid substitutions influence ice plane selectivity and antifreeze activity.
PMID: 28956610
DOI: 10.1021/acs.jpcb.7b06619
1. The influence of the adsorption orientation of type I antifreeze proteins on their thermal hysteresis temperature is significant and cannot be ignored.
2. The influence of the adsorption orientation on the thermal hysteresis effect of AFP9 and HPLC-6 is more obvious than that of AAAA2kE.

AFP011009055

Mutation A17L
Sequence
Ice crystal morphology
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP(A17L)
Ice crystal morphology Fig.4 Ice crystal morphology of the type I AFP variants. Ice crystals were formed in the presence of 9 mg/ml A17L and A21L, or 1 mg/ml A19L and A20L in 0.1 M NH4HCO3 (pH 7.9). A17L and A21L images were taken after 0.02℃ undercooling; the A19L and A20L images were taken after 0.2℃ undercooling.
Thermal Hysteresis
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP(A17L)
Thermal Hysteresis Fig.3. Thermal hysteresis activity as a function of the concentration of A17L (open circles), A19L (closed circles), A20L (open squares), A21L (closed squares) and wild-type (open triangles). Each data point represents the mean of at least three determinations and the vertical bars represent the S.D.
Brief description
PMID: 10601644
DOI: 10.1016/s0014-5793(99)01588-4
1. The traditional ice-binding surface of type I AFP (involving Leu, Asn, and the Thr OH group) may be misidentified. The new binding face encompasses the conserved Ala-rich surface and adjacent Thr.
2. Mutational studies of Ala to Leu in type I AFP showed that the Ala17 mutation (A17L) completely lost antifreeze activity, the Ala21 mutation (A21L) had weak antifreeze activity, and the Ala19 (A19L) and Ala20 (A20L) mutations retained wild-type activity.
3. The γ-gmethyl group of Thr is essential for the ice-binding activity of type I AFP, as demonstrated by the retention of activity in Thr to Val substitutions.

AFP011009056

Mutation A19L
Sequence
Ice crystal morphology
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP(A19L)
Ice crystal morphology Fig.4 Ice crystal morphology of the type I AFP variants. Ice crystals were formed in the presence of 9 mg/ml A17L and A21L, or 1 mg/ml A19L and A20L in 0.1 M NH4HCO3 (pH 7.9). A17L and A21L images were taken after 0.02℃ undercooling; the A19L and A20L images were taken after 0.2℃ undercooling.
Thermal Hysteresis
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP(A19L)
Thermal Hysteresis Fig.3. Thermal hysteresis activity as a function of the concentration of A17L (open circles), A19L (closed circles), A20L (open squares), A21L (closed squares) and wild-type (open triangles). Each data point represents the mean of at least three determinations and the vertical bars represent the S.D.
Brief description
PMID: 10601644
DOI: 10.1016/s0014-5793(99)01588-4
1. The traditional ice-binding surface of type I AFP (involving Leu, Asn, and the Thr OH group) may be misidentified. The new binding face encompasses the conserved Ala-rich surface and adjacent Thr.
2. Mutational studies of Ala to Leu in type I AFP showed that the Ala17 mutation (A17L) completely lost antifreeze activity, the Ala21 mutation (A21L) had weak antifreeze activity, and the Ala19 (A19L) and Ala20 (A20L) mutations retained wild-type activity.
3. The γ-gmethyl group of Thr is essential for the ice-binding activity of type I AFP, as demonstrated by the retention of activity in Thr to Val substitutions.

AFP011009057

Mutation A20L
Sequence
Ice crystal morphology
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP(A20L)
Ice crystal morphology Fig.4 Ice crystal morphology of the type I AFP variants. Ice crystals were formed in the presence of 9 mg/ml A17L and A21L, or 1 mg/ml A19L and A20L in 0.1 M NH4HCO3 (pH 7.9). A17L and A21L images were taken after 0.02℃ undercooling; the A19L and A20L images were taken after 0.2℃ undercooling.
Thermal Hysteresis
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP(A20L)
Thermal Hysteresis Fig.3. Thermal hysteresis activity as a function of the concentration of A17L (open circles), A19L (closed circles), A20L (open squares), A21L (closed squares) and wild-type (open triangles). Each data point represents the mean of at least three determinations and the vertical bars represent the S.D.
Brief description
PMID: 10601644
DOI: 10.1016/s0014-5793(99)01588-4
1. The traditional ice-binding surface of type I AFP (involving Leu, Asn, and the Thr OH group) may be misidentified. The new binding face encompasses the conserved Ala-rich surface and adjacent Thr.
2. Mutational studies of Ala to Leu in type I AFP showed that the Ala17 mutation (A17L) completely lost antifreeze activity, the Ala21 mutation (A21L) had weak antifreeze activity, and the Ala19 (A19L) and Ala20 (A20L) mutations retained wild-type activity.
3. The γ-gmethyl group of Thr is essential for the ice-binding activity of type I AFP, as demonstrated by the retention of activity in Thr to Val substitutions.

AFP011009058

Mutation A21L
Sequence
Ice crystal morphology
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP(A21L)
Ice crystal morphology Fig.4 Ice crystal morphology of the type I AFP variants. Ice crystals were formed in the presence of 9 mg/ml A17L and A21L, or 1 mg/ml A19L and A20L in 0.1 M NH4HCO3 (pH 7.9). A17L and A21L images were taken after 0.02℃ undercooling; the A19L and A20L images were taken after 0.2℃ undercooling.
Thermal Hysteresis
PMID 10601644
DOI 10.1016/s0014-5793(99)01588-4
Protein Name winter flounder AFP(A21L)
Thermal Hysteresis Fig.3. Thermal hysteresis activity as a function of the concentration of A17L (open circles), A19L (closed circles), A20L (open squares), A21L (closed squares) and wild-type (open triangles). Each data point represents the mean of at least three determinations and the vertical bars represent the S.D.
Brief description
PMID: 10601644
DOI: 10.1016/s0014-5793(99)01588-4
1. The traditional ice-binding surface of type I AFP (involving Leu, Asn, and the Thr OH group) may be misidentified. The new binding face encompasses the conserved Ala-rich surface and adjacent Thr.
2. Mutational studies of Ala to Leu in type I AFP showed that the Ala17 mutation (A17L) completely lost antifreeze activity, the Ala21 mutation (A21L) had weak antifreeze activity, and the Ala19 (A19L) and Ala20 (A20L) mutations retained wild-type activity.
3. The γ-gmethyl group of Thr is essential for the ice-binding activity of type I AFP, as demonstrated by the retention of activity in Thr to Val substitutions.

AFP011009059

Mutation N16A,N27A
Sequence
Ice crystal morphology
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAA)
Ice crystal morphology Fig.4 Ice crystal morphologies of type I AFP mutants. Ice crystals were formed in the presence of approximately 1 mg/mL variant AFPs at 0.1 ℃ cooling.
Thermal Hysteresis
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAA)
Thermal Hysteresis Fig.3.A Asn replacement variants: thermal hysteresis activities of wild-type HPLC-6 (LTAAN) (O), variants LTAAT (●), LTAAA (□), LTAAV (■), and LTAAQ (△) were compared over a range of concentrations.
Brief description
PMID: 10200162
DOI: 10.1021/bi982602p
1. Leu plays a crucial role in preventing the aggregation of alanine-rich helices at in vivo concentrations.
2. Asn may be more important for increasing peptide solubility than for binding to ice through traditional hydrogen bonding and/or steric complementarity.
3. The complete elimination of thermal hysteresis activity after replacing Asn with Gln (LTAAQ) having a larger side chain indicates that Asn may be in contact with the ice surface when type I antifreeze protein binds to the ice lattice.
4. The variant with the introduced ATAAT ice-binding motif (IBM) had higher activity than the wild type when solubility was maintained, but this might be due to the increased number of ice-binding repeats

AFP011009060

Mutation N16T,N27T
Sequence
Ice crystal morphology
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAT)
Ice crystal morphology Fig.4 Ice crystal morphologies of type I AFP mutants. Ice crystals were formed in the presence of approximately 1 mg/mL variant AFPs at 0.1 ℃ cooling.
Thermal Hysteresis
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAT)
Thermal Hysteresis Fig.3.A Asn replacement variants: thermal hysteresis activities of wild-type HPLC-6 (LTAAN) (O), variants LTAAT (●), LTAAA (□), LTAAV (■), and LTAAQ (△) were compared over a range of concentrations.
Brief description
PMID: 10200162
DOI: 10.1021/bi982602p
1. Leu plays a crucial role in preventing the aggregation of alanine-rich helices at in vivo concentrations.
2. Asn may be more important for increasing peptide solubility than for binding to ice through traditional hydrogen bonding and/or steric complementarity.
3. The complete elimination of thermal hysteresis activity after replacing Asn with Gln (LTAAQ) having a larger side chain indicates that Asn may be in contact with the ice surface when type I antifreeze protein binds to the ice lattice.
4. The variant with the introduced ATAAT ice-binding motif (IBM) had higher activity than the wild type when solubility was maintained, but this might be due to the increased number of ice-binding repeats

AFP011009061

Mutation N16V,N27V
Sequence
Ice crystal morphology
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAV)
Ice crystal morphology Fig.4 Ice crystal morphologies of type I AFP mutants. Ice crystals were formed in the presence of approximately 1 mg/mL variant AFPs at 0.1 ℃ cooling.
Thermal Hysteresis
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAV)
Thermal Hysteresis Fig.3.A Asn replacement variants: thermal hysteresis activities of wild-type HPLC-6 (LTAAN) (O), variants LTAAT (●), LTAAA (□), LTAAV (■), and LTAAQ (△) were compared over a range of concentrations.
Brief description
PMID: 10200162
DOI: 10.1021/bi982602p
1. Leu plays a crucial role in preventing the aggregation of alanine-rich helices at in vivo concentrations.
2. Asn may be more important for increasing peptide solubility than for binding to ice through traditional hydrogen bonding and/or steric complementarity.
3. The complete elimination of thermal hysteresis activity after replacing Asn with Gln (LTAAQ) having a larger side chain indicates that Asn may be in contact with the ice surface when type I antifreeze protein binds to the ice lattice.
4. The variant with the introduced ATAAT ice-binding motif (IBM) had higher activity than the wild type when solubility was maintained, but this might be due to the increased number of ice-binding repeats

AFP011009062

Mutation N16Q,N27Q
Sequence
Ice crystal morphology
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAQ)
Ice crystal morphology Fig.4 Ice crystal morphologies of type I AFP mutants. Ice crystals were formed in the presence of approximately 1 mg/mL variant AFPs at 0.1 ℃ cooling.
Thermal Hysteresis
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(LTAAQ)
Thermal Hysteresis Fig.3.A Asn replacement variants: thermal hysteresis activities of wild-type HPLC-6 (LTAAN) (O), variants LTAAT (●), LTAAA (□), LTAAV (■), and LTAAQ (△) were compared over a range of concentrations.
Brief description
PMID: 10200162
DOI: 10.1021/bi982602p
1. Leu plays a crucial role in preventing the aggregation of alanine-rich helices at in vivo concentrations.
2. Asn may be more important for increasing peptide solubility than for binding to ice through traditional hydrogen bonding and/or steric complementarity.
3. The complete elimination of thermal hysteresis activity after replacing Asn with Gln (LTAAQ) having a larger side chain indicates that Asn may be in contact with the ice surface when type I antifreeze protein binds to the ice lattice.
4. The variant with the introduced ATAAT ice-binding motif (IBM) had higher activity than the wild type when solubility was maintained, but this might be due to the increased number of ice-binding repeats

AFP011009063

Mutation L12A,N16A,L23A,N27A
Sequence
Ice crystal morphology
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(ATAAA)
Ice crystal morphology Fig.4 Ice crystal morphologies of type I AFP mutants. Ice crystals were formed in the presence of approximately 1 mg/mL variant AFPs at 0.1 ℃ cooling.
Thermal Hysteresis
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(ATAAA)
Thermal Hysteresis Fig.3.B Leu replacement variants: thermal hysteresis activities of ATAAT (●), ATAAN (O), and ATAAA (■) were compared over a range of concentrations. For reference, the activity profiles of their Leu-containing counterparts LTAAT (●), LTAAN (O), and LTAAA (□) are shown linked by dotted lines.
Brief description
PMID: 10200162
DOI: 10.1021/bi982602p
1. Leu plays a crucial role in preventing the aggregation of alanine-rich helices at in vivo concentrations.
2. Asn may be more important for increasing peptide solubility than for binding to ice through traditional hydrogen bonding and/or steric complementarity.
3. The complete elimination of thermal hysteresis activity after replacing Asn with Gln (LTAAQ) having a larger side chain indicates that Asn may be in contact with the ice surface when type I antifreeze protein binds to the ice lattice.
4. The variant with the introduced ATAAT ice-binding motif (IBM) had higher activity than the wild type when solubility was maintained, but this might be due to the increased number of ice-binding repeats

AFP011009064

Mutation L12A,N16T,L23A,N27T
Sequence
Ice crystal morphology
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(ATAAT)
Ice crystal morphology Fig.4 Ice crystal morphologies of type I AFP mutants. Ice crystals were formed in the presence of approximately 1 mg/mL variant AFPs at 0.1 ℃ cooling.
Thermal Hysteresis
PMID 10200162
DOI 10.1021/bi982602p
Protein Name winter flounder AFP(ATAAT)
Thermal Hysteresis Fig.3.B Leu replacement variants: thermal hysteresis activities of ATAAT (●), ATAAN (O), and ATAAA (■) were compared over a range of concentrations. For reference, the activity profiles of their Leu-containing counterparts LTAAT (●), LTAAN (O), and LTAAA (□) are shown linked by dotted lines.
Brief description
PMID: 10200162
DOI: 10.1021/bi982602p
1. Leu plays a crucial role in preventing the aggregation of alanine-rich helices at in vivo concentrations.
2. Asn may be more important for increasing peptide solubility than for binding to ice through traditional hydrogen bonding and/or steric complementarity.
3. The complete elimination of thermal hysteresis activity after replacing Asn with Gln (LTAAQ) having a larger side chain indicates that Asn may be in contact with the ice surface when type I antifreeze protein binds to the ice lattice.
4. The variant with the introduced ATAAT ice-binding motif (IBM) had higher activity than the wild type when solubility was maintained, but this might be due to the increased number of ice-binding repeats

AFP011009065

Mutation A33W
Sequence
Thermal Hysteresis
PMID 22853917
DOI 10.1016/j.bpj.2012.06.013
Protein Name winter flounder AFP(TATW)
Thermal Hysteresis Fig.1 Freezing point hysteresis in 100 mM NH4HCO3 buffer.TATW (Green filled circles).
Brief description
PMID: 22853917
DOI: 10.1016/j.bpj.2012.06.013
1. The pseudo-wild-type TATW and its three mutants TLTW, SASW, VAVW of winter flounder antifreeze peptide (wf-AFP1) were synthesized, and their thermal hysteresis activities were determined by freezing point hysteresis experiments. The activity ranking was found to be TATA>TATW>VAVA>VAVW>WLTW>SASW.
2. Circular dichroism (CD) experiments SASW showed that although had a high helix content at room temperature, its activity was low. The helix content of TATW, TLTW, and VAVA increased at and their activities were higher than that of SASW, indicating that a large helix content does not guarantee activity.
3. Short-range ice binding and long-range solvent perturbation are two mechanisms related to the activity of antifreeze proteins and glycoproteins. The results showed that the short-range model can explain the activity of mutants, while the long-range model is a necessary condition for activity, as the most active peptides all have an extended dynamical hydration shell. It seems that antifreeze proteins and glycoproteins have evolved different solutions to the antifreeze problem.

AFP011009066

Mutation A17L,A33W
Sequence
Thermal Hysteresis
PMID 22853917
DOI 10.1016/j.bpj.2012.06.013
Protein Name winter flounder AFP(TLTW)
Thermal Hysteresis Fig.1 Freezing point hysteresis in 100 mM NH4HCO3 buffer.TLTW (Blue Fileed square).
Brief description
PMID: 22853917
DOI: 10.1016/j.bpj.2012.06.013
1. The pseudo-wild-type TATW and its three mutants TLTW, SASW, VAVW of winter flounder antifreeze peptide (wf-AFP1) were synthesized, and their thermal hysteresis activities were determined by freezing point hysteresis experiments. The activity ranking was found to be TATA>TATW>VAVA>VAVW>WLTW>SASW.
2. Circular dichroism (CD) experiments SASW showed that although had a high helix content at room temperature, its activity was low. The helix content of TATW, TLTW, and VAVA increased at and their activities were higher than that of SASW, indicating that a large helix content does not guarantee activity.
3. Short-range ice binding and long-range solvent perturbation are two mechanisms related to the activity of antifreeze proteins and glycoproteins. The results showed that the short-range model can explain the activity of mutants, while the long-range model is a necessary condition for activity, as the most active peptides all have an extended dynamical hydration shell. It seems that antifreeze proteins and glycoproteins have evolved different solutions to the antifreeze problem.

AFP011009067

Mutation T13S,T24S,A33W
Sequence
Thermal Hysteresis
PMID 22853917
DOI 10.1016/j.bpj.2012.06.013
Protein Name winter flounder AFP(SASW)
Thermal Hysteresis Fig.1 Freezing point hysteresis in 100 mM NH4HCO3 buffer.SASW (Red Fileed Triangle).
Brief description
PMID: 22853917
DOI: 10.1016/j.bpj.2012.06.013
1. The pseudo-wild-type TATW and its three mutants TLTW, SASW, VAVW of winter flounder antifreeze peptide (wf-AFP1) were synthesized, and their thermal hysteresis activities were determined by freezing point hysteresis experiments. The activity ranking was found to be TATA>TATW>VAVA>VAVW>WLTW>SASW.
2. Circular dichroism (CD) experiments SASW showed that although had a high helix content at room temperature, its activity was low. The helix content of TATW, TLTW, and VAVA increased at and their activities were higher than that of SASW, indicating that a large helix content does not guarantee activity.
3. Short-range ice binding and long-range solvent perturbation are two mechanisms related to the activity of antifreeze proteins and glycoproteins. The results showed that the short-range model can explain the activity of mutants, while the long-range model is a necessary condition for activity, as the most active peptides all have an extended dynamical hydration shell. It seems that antifreeze proteins and glycoproteins have evolved different solutions to the antifreeze problem.

AFP011009068

Mutation T2I,T13I,T24I,T35I,A7K,A11E,A29K,A33E
Sequence
Ice crystal morphology
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(IIII2KE)
Ice crystal morphology Fig.2 Video microscopy images of ice crystal growth in the presence of (a) BBBB2KE, (b) IIII2KE, (c) TTTTAL2KE and (d) VVVVAL2KE. All concentrations are in the range 6-7 mM.
Thermal Hysteresis
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(IIII2KE)
Thermal Hysteresis "Further addition of another methyl group to give IIII2KE gives no thermal hysteresis."
Brief description
PMID: 11240143
DOI: 10.1016/s0014-5793(01)02213-x
1. The γ-methyl group of threonine alone is not sufficient to confer ice-growth inhibition properties. The presence of the OH group and the γ-methyl in TTTT, or an additional methyl group like in VVVV2KE, confers significantly higher thermal hysteresis.
2. The IIII2KE with isoleucine replacing threonine can modify the ice crystal shape but shows no thermal hysteresis, indicating that replacing the hydroxyl group of threonine in TTTT with an ethyl group removes the ability to inhibit ice growth.
3. TTTTAL2KE and VVVVAL2KE with mutations in aspartic acid (Asp) and asparagine (Asn) show no thermal hysteresis, confirming the involvement of these Asx residues in the ice - growth inhibition mechanism.

AFP011009069

Mutation D1A,D5A,N16L,N27L,A7K,A11E,A29K,A33E
Sequence
Ice crystal morphology
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(TTTTAL2KE)
Ice crystal morphology Fig.2 Video microscopy images of ice crystal growth in the presence of (a) BBBB2KE, (b) IIII2KE, (c) TTTTAL2KE and (d) VVVVAL2KE. All concentrations are in the range 6-7 mM.
Thermal Hysteresis
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(TTTTAL2KE)
Thermal Hysteresis ”Of the four polypeptides, only BBBB2KE showed thermal hysteresis.“
Brief description
PMID: 11240143
DOI: 10.1016/s0014-5793(01)02213-x
1. The γ-methyl group of threonine alone is not sufficient to confer ice-growth inhibition properties. The presence of the OH group and the γ-methyl in TTTT, or an additional methyl group like in VVVV2KE, confers significantly higher thermal hysteresis.
2. The IIII2KE with isoleucine replacing threonine can modify the ice crystal shape but shows no thermal hysteresis, indicating that replacing the hydroxyl group of threonine in TTTT with an ethyl group removes the ability to inhibit ice growth.
3. TTTTAL2KE and VVVVAL2KE with mutations in aspartic acid (Asp) and asparagine (Asn) show no thermal hysteresis, confirming the involvement of these Asx residues in the ice - growth inhibition mechanism.

AFP011009070

Mutation D1A,T2V,D5A,T13V,N16L,N27L,T24V,T35V,A7K,A11K,A29K,A33E
Sequence
Ice crystal morphology
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(VVVVAL2KE)
Ice crystal morphology Fig.2 Video microscopy images of ice crystal growth in the presence of (a) BBBB2KE, (b) IIII2KE, (c) TTTTAL2KE and (d) VVVVAL2KE. All concentrations are in the range 6-7 mM.
Thermal Hysteresis
PMID 11240143
DOI 10.1016/s0014-5793(01)02213-x
Protein Name winter flounder AFP(VVVVAL2KE)
Thermal Hysteresis ”Of the four polypeptides, only BBBB2KE showed thermal hysteresis.“
Brief description
PMID: 11240143
DOI: 10.1016/s0014-5793(01)02213-x
1. The γ-methyl group of threonine alone is not sufficient to confer ice-growth inhibition properties. The presence of the OH group and the γ-methyl in TTTT, or an additional methyl group like in VVVV2KE, confers significantly higher thermal hysteresis.
2. The IIII2KE with isoleucine replacing threonine can modify the ice crystal shape but shows no thermal hysteresis, indicating that replacing the hydroxyl group of threonine in TTTT with an ethyl group removes the ability to inhibit ice growth.
3. TTTTAL2KE and VVVVAL2KE with mutations in aspartic acid (Asp) and asparagine (Asn) show no thermal hysteresis, confirming the involvement of these Asx residues in the ice - growth inhibition mechanism.

AFP011009071

Mutation L12C
Sequence
Ice crystal morphology
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (L12C)
Tag spin
Ice crystal morphology Fig.4.B L12C at a concentration of 8.0 mg/ml at -0.08,-0.34,and-0.52℃, respectively,from left to right.
Thermal Hysteresis
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (L12C)
Tag spin
Thermal Hysteresis Fig.3 Antifreeze activity of the wild-type type-I AFP (black squares), spin-labeled L23C (red discs), spin-labeled L12C (blue, upward-pointing triangles), spin-labeled A20C (purple, downward-pointing triangles), spin-labeled A11C (green diamonds), and spin-labeled A17C (navy blue, leftward-pointing triangles). HPLC6 spin-labeled L23C (red discs)
Brief description
PMID: 29487966
DOI: 10.1007/s00249-018-1285-3
1. The putative ice-binding surface (IBS) of type-I AFPs, which consists of Thr side chains and conserved i+4 and i+8 Ala side chains, is crucial for their antifreeze functions.
2. Type-I AFPs can inhibit the nucleation of seed ice crystals, allowing solutions to stay in super-cooled states at lower temperatures.
3. A proposed antifreeze mechanism of AFPs involves the formation of a water-AFP-ice (WAI) interphase, which reduces ice-water interfacial tension, enhances the local colligative effect, and interrupts water molecules from joining the ice lattice.

AFP011009072

Mutation L23C
Sequence
Ice crystal morphology
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (L23C)
Tag spin
Ice crystal morphology Fig.4.A L23C at a concentration of 8.0 mg/ml at -0.15,-0.63,and-0.72℃, respectively,from left to right.
Thermal Hysteresis
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (L23C)
Tag spin
Thermal Hysteresis Fig.3 Antifreeze activity of the wild-type type-I AFP (black squares), spin-labeled L23C (red discs), spin-labeled L12C (blue, upward-pointing triangles), spin-labeled A20C (purple, downward-pointing triangles), spin-labeled A11C (green diamonds), and spin-labeled A17C (navy blue, leftward-pointing triangles). HPLC6 spin-labeled L12C (blue, upward-pointing triangles)
Brief description
PMID: 29487966
DOI: 10.1007/s00249-018-1285-3
1. The putative ice-binding surface (IBS) of type-I AFPs, which consists of Thr side chains and conserved i+4 and i+8 Ala side chains, is crucial for their antifreeze functions.
2. Type-I AFPs can inhibit the nucleation of seed ice crystals, allowing solutions to stay in super-cooled states at lower temperatures.
3. A proposed antifreeze mechanism of AFPs involves the formation of a water-AFP-ice (WAI) interphase, which reduces ice-water interfacial tension, enhances the local colligative effect, and interrupts water molecules from joining the ice lattice.

AFP011009073

Mutation A20C
Sequence
Ice crystal morphology
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (A20C)
Tag spin
Ice crystal morphology Fig.4.C L23C at a concentration of 8.0 mg/ml at -0.10,-0.65,and-0.74℃, respectively,from left to right.
Thermal Hysteresis
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (A20C)
Tag spin
Thermal Hysteresis Fig.3 Antifreeze activity of the wild-type type-I AFP (black squares), spin-labeled L23C (red discs), spin-labeled L12C (blue, upward-pointing triangles), spin-labeled A20C (purple, downward-pointing triangles), spin-labeled A11C (green diamonds), and spin-labeled A17C (navy blue, leftward-pointing triangles). HPLC6 spin-labeled A20C (purple, downward-pointing triangles)
Brief description
PMID: 29487966
DOI: 10.1007/s00249-018-1285-3
1. The putative ice-binding surface (IBS) of type-I AFPs, which consists of Thr side chains and conserved i+4 and i+8 Ala side chains, is crucial for their antifreeze functions.
2. Type-I AFPs can inhibit the nucleation of seed ice crystals, allowing solutions to stay in super-cooled states at lower temperatures.
3. A proposed antifreeze mechanism of AFPs involves the formation of a water-AFP-ice (WAI) interphase, which reduces ice-water interfacial tension, enhances the local colligative effect, and interrupts water molecules from joining the ice lattice.

AFP011009074

Mutation A11C
Sequence
Ice crystal morphology
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (A11C)
Tag spin
Ice crystal morphology Fig.4.D L23C at a concentration of 8.0 mg/ml at -0.05,-0.23,and-38℃, respectively,from left to right.
Thermal Hysteresis
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (A11C)
Tag spin
Thermal Hysteresis Fig.3 Antifreeze activity of the wild-type type-I AFP (black squares), spin-labeled L23C (red discs), spin-labeled L12C (blue, upward-pointing triangles), spin-labeled A20C (purple, downward-pointing triangles), spin-labeled A11C (green diamonds), and spin-labeled A17C (navy blue, leftward-pointing triangles). HPLC6 spin-labeled A11C (green diamonds)
Brief description
PMID: 29487966
DOI: 10.1007/s00249-018-1285-3
1. The putative ice-binding surface (IBS) of type-I AFPs, which consists of Thr side chains and conserved i+4 and i+8 Ala side chains, is crucial for their antifreeze functions.
2. Type-I AFPs can inhibit the nucleation of seed ice crystals, allowing solutions to stay in super-cooled states at lower temperatures.
3. A proposed antifreeze mechanism of AFPs involves the formation of a water-AFP-ice (WAI) interphase, which reduces ice-water interfacial tension, enhances the local colligative effect, and interrupts water molecules from joining the ice lattice.

AFP011009075

Mutation A17C
Sequence
Ice crystal morphology
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (A17C)
Tag spin
Ice crystal morphology Fig.4.E L23C at a concentration of 8.0 mg/ml at -0.01,-0.02,and-0.02℃, respectively,from left to right(top) and -0.02,-0.01,and-0.02℃, respectively,from left to right(down).
Thermal Hysteresis
PMID 29487966
DOI 10.1007/s00249-018-1285-3
Protein Name winter flounder AFP HPLC6 (A17C)
Tag spin
Thermal Hysteresis Fig.3 Antifreeze activity of the wild-type type-I AFP (black squares), spin-labeled L23C (red discs), spin-labeled L12C (blue, upward-pointing triangles), spin-labeled A20C (purple, downward-pointing triangles), spin-labeled A11C (green diamonds), and spin-labeled A17C (navy blue, leftward-pointing triangles). HPLC6 spin-labeled A17C (navy blue, leftward-pointing triangles)
Brief description
PMID: 29487966
DOI: 10.1007/s00249-018-1285-3
1. The putative ice-binding surface (IBS) of type-I AFPs, which consists of Thr side chains and conserved i+4 and i+8 Ala side chains, is crucial for their antifreeze functions.
2. Type-I AFPs can inhibit the nucleation of seed ice crystals, allowing solutions to stay in super-cooled states at lower temperatures.
3. A proposed antifreeze mechanism of AFPs involves the formation of a water-AFP-ice (WAI) interphase, which reduces ice-water interfacial tension, enhances the local colligative effect, and interrupts water molecules from joining the ice lattice.

AFP011009076

Mutation T2S,A17L,T24S,T35S
Sequence
Ice crystal morphology
PMID 37956730
DOI 10.1016/j.bbapap.2023.140973
Protein Name winter flounder AFP (MutAFP)
Ice crystal morphology Fig.2 Antifreeze activity of E. coli-expressed proteins. Panel A. Ice crystals formed in the presence of 1.5 mM His-SUMO, MutAFP6, His-SUMO-AFP6 and AFP6 in 10 mM NH4HCO3 and buffer alone. Images are labeled with the protein name, or buffer for the buffer control. Each is representative of crystals in a minimum of 3 samples. The white line in each image represents 50 μm.
Thermal Hysteresis
PMID 37956730
DOI 10.1016/j.bbapap.2023.140973
Protein Name winter flounder AFP (MutAFP)
Thermal Hysteresis Fig.2 Antifreeze activity of E. coli-expressed proteins. Panel B. Concentration-dependent thermal hysteresis of His-SUMO, MutAFP6, His-SUMO-AFP6 and AFP6. Measurements were performed on each protein and background values for the buffer control were subtracted. Values shown are means ±SD for triplicate samples.
Brief description
PMID: 37956730
DOI: 10.1016/j.bbapap.2023.140973
1. AFP6 can change from an ice nucleation inhibitor to a nucleator as the temperature drops, and this dual-effect is not observed in other tested proteins.
2. AFP6 exhibits strong TH activity and forms bipyramidal ice crystals, while a mutant variant (MutAFP6) with four point mutations (T2S, A17L, T24S, T35S) loses this activity and alters ice crystal morphology.
3. The ice nucleation activity of AFP6 is concentration-dependent, reaching its maximum at 1.5 mM.
4. The fusion protein of AFP6, His-SUMO-AFP6, has thermal hysteresis activity but no ice nucleation activity, indicating that the fusion moiety may inhibit the protein assembly required for AFP6 nucleation.

AFP011009077

Mutation Wild Type
Sequence
Ice crystal morphology
PMID 2687848
DOI 10.1093/protein/3.2.145
Protein Name winter flounder proAFP-6
Ice crystal morphology Fig.8 (B) Ice crystals grown from solutions of 5 mg/ml bacterial proAFP (Bact.), 5 mg/ml natural proAFP (W.F.) and 10 mg/ml bovine serum albumin (Cont.).
Thermal Hysteresis
PMID 2687848
DOI 10.1093/protein/3.2.145
Protein Name winter flounder proAFP-6
Thermal Hysteresis Fig.8.A Antifreeze activity curves of the β-gal-proAFP fusion protein (Fus.), proAFP isolated from winter flounder (W.F.) and bacterial proAFP (Bact.). Each point represents the average of at least four hysteresis and duplicate proAFP concentration measurements.
Thermal Hysteresis
PMID 3769927
DOI 10.1111/j.1432-1033.1986.tb09966.x
Protein Name winter flounder proAFP-6
Thermal Hysteresis Fig.3 The antifreeze activity of flounder pro-antifreezes plotted against concentration by mass ( A ) and against molar concentration ( B ) . Various amounts of proAFP-6, proAFP-8 and AFP-6 were dissolved in 0.01 M NH4HC03. Thermal hystereses of these materials were measured using a nanoliter osmometer. Each point, which is an average of four measurements, has a deviation of ±0.01℃.
Brief description
PMID: 2687848
DOI: 10.1093/protein/3.2.145
1. The fusion protein proAFP-6, expressed with a β-galactosidase tag and later cleaved by Factor Xa, retains its α-helical structure and exhibits the same thermal hysteresis (TH) activity as the natural AFP.
2. The α-helix content of proAFP affects its antifreeze activity, and the α-helix content of the mature region may increase after processing.
3. The pro segment of proAFP may partially block its hydrogen bonding with ice crystals, thus affecting the antifreeze activity.
4. The recombinant AFP induces typical hexagonal bipyramidal ice crystal formation but does not show ice recrystallization inhibition (IRI) activity, confirming its primary antifreeze function through TH activity.
PMID: 3769927
DOI: 10.1111/j.1432-1033.1986.tb09966.x
1. Two major pro-antifreezes corresponding to the precursors for AFP-6 and AFP-8 were isolated and characterized from winter flounder liver.
2. The pro-antifreezes were synthesized in the liver seasonally, starting in October and ceasing in March.
3. Both proAFP-6 and proAFP-8 showed antifreeze activity, but their activities were lower than those of the mature AFP.

AFP011009078

Mutation 1_23del
Sequence
Ice crystal morphology
PMID 17868093
DOI 10.1002/bip.20844
Protein Name HK-1
Ice crystal morphology Fig.6 Light microscope images of ice crystals growing from solutions of pure water and HK-2 (10 mg/mL).
Thermal Hysteresis
PMID 17868093
DOI 10.1002/bip.20844
Protein Name HK-1
Thermal Hysteresis Fig.4 Thermal hysteresis measurements of AFP fragment solutions (A) HK-1, (B) HK-3, (C) HK-2.
Thermal Hysteresis
PMID N/A
DOI 10.1016/j.ejbt.2022.08.003
Protein Name AQ4744
Thermal Hysteresis Fig.5 Thermal hysteresis activity. A. The activity for homopeptide series and reference peptides at four different concentrations is presented. Color code is as follows: Lys series orange, Arg series blue, Proline series green. The peptide used as a negative control is in grey, and reference peptides are in red, blue and magenta. The colors are on a scale from light to dark depending on the concentration used: 2, 10, 15 or 25 mM. B. Comparison of the peptide vs AQ1317 (black bars) according to concentration. The homopeptide series are plotted in light to dark color according to the number of residues (7–14), and reference peptides are in red, dark blue and magenta. Significant differences are indicated at ** P < 0.01, *** P < 0.001, **** P < 0.0002.
Brief description
PMID: 17868093
DOI: 10.1002/bip.20844
1. Short segments of Type I AFP, particularly HK-2, exhibit significant thermal hysteresis activity, achieving up to 60% of the native protein's activity.
2. Antifreeze activity is highly dependent on amino acid sequence and secondary structure, with α-helix content being crucial for effectiveness.
DOI: 10.1016/j.ejbt.2022.08.003
1. Short homopeptides can form a type II polyproline helix secondary structure, which is more stable at low temperatures.
2. Intermediate - length homopeptides and proline homopeptides have higher thermal hysteresis activity.
3. Studying homopeptides helps to reveal the mechanism of antifreeze activity and is beneficial for designing new antifreeze molecules.

AFP011009079

Mutation 13_37del
Sequence
Ice crystal morphology
PMID 29276886
DOI 10.1021/acsami.7b13130
Protein Name peptide 1-1
Ice crystal morphology Fig.2 (a) Optical microscopic images of the ice crystal morphologies grown in pure water and the solutions of peptides 1-1, 1-2, and 1-3. (b) Optical images of the ice crystal grown in PBS buffer and peptide solutions. The scale bar is 100 μm.
Thermal Hysteresis
PMID 17868093
DOI 10.1002/bip.20844
Protein Name HK-2
Thermal Hysteresis Fig.4 Thermal hysteresis measurements of AFP fragment solutions (A) HK-1, (B) HK-3, (C) HK-2.
Thermal Hysteresis
PMID 29276886
DOI 10.1021/acsami.7b13130
Protein Name peptide 1-1
Thermal Hysteresis Fig.S4 The thermal hysteresis of peptide 1-1 at different concentration.
Ice Recrystallization Inhibition
PMID 29276886
DOI 10.1021/acsami.7b13130
Protein Name peptide 1-1
Ice Recrystallization Inhibition "However, the peptides 1-1 and 1-3 do not exhibit IRI activity."
Ice Grow Rate
PMID 40358480
DOI 10.1021/jacs.4c18537
Protein Name Peptide 14
Ice Grow Rate Fig.4 Ability of AFPTs to inhibit ice growth. (a) Growth processes of single ice crystals in H2O, E-1, E-2, E-3, E-4, and E-5 aqueous dispersions. (b) Quantitative assessment of ice growth rates in different aqueous dispersions. (c) Structures of AGPS, E-6, and E-7. (d) Growth processes of single ice crystals in AGPS, E-6, and E-7 aqueous dispersions. (e) Ice growth rates of >100 AFPTs aqueous solutions. Scale bar: 100 μm.
Brief description
PMID: 17868093
DOI: 10.1002/bip.20844
1. Short segments of Type I AFP, particularly HK-2, exhibit significant thermal hysteresis activity, achieving up to 60% of the native protein's activity.
2. Antifreeze activity is highly dependent on amino acid sequence and secondary structure, with α-helix content being crucial for effectiveness.
PMID: 29276886
DOI: 10.1021/acsami.7b13130
1. This study designs three 12-amino acid α-helical antifreeze peptides inspired by type I AFP to investigate their antifreeze properties.
2. Different antifreeze peptides have different effects on ice crystal morphology. Peptides 1-1 and 1-2 can modify the ice crystal morphology, while peptide 1-3 has no such effect.
3. The ice recrystallization inhibition activities of antifreeze peptides are different. Peptide 1-2 has this activity, while peptides 1-1 and 1-3 do not.
PMID: 40358480
DOI: 10.1021/jacs.4c18537
1. Glutamic acid (E) is identified as the strongest ice-binding site (IBS)​, with 4-fold higher binding energy than natural IBSs like threonine (T), enabling significant enhancement of antifreeze activity in designed peptides.
2. ​A "Site to Distance" principle is established for de novo design of AFPTs, involving incorporation of E residues and tuning distances between IBSs to match ice crystal lattices (e.g., 6.4 Å for 1.5 lattices on the prism plane), resulting in superior ice growth inhibition.
3. Designed AFPTs (e.g., E-2 and triE) exhibit exceptional ice growth inhibition and thermal hysteresis (TH) activity, outperforming over 100 natural or previously reported AFPTs, with applications in cell cryopreservation showing high post-thaw viability.

AFP011009080

Mutation 1_13del,
Sequence
Thermal Hysteresis
PMID 17868093
DOI 10.1002/bip.20844
Protein Name HK-3
Thermal Hysteresis Fig.4 Thermal hysteresis measurements of AFP fragment solutions (A) HK-1, (B) HK-3, (C) HK-2.
Brief description
PMID: 17868093
DOI: 10.1002/bip.20844
1. Short segments of Type I AFP, particularly HK-2, exhibit significant thermal hysteresis activity, achieving up to 60% of the native protein's activity.
2. Antifreeze activity is highly dependent on amino acid sequence and secondary structure, with α-helix content being crucial for effectiveness.

AFP011009081

Mutation A7K,A11E,13_37del
Sequence
Ice crystal morphology
PMID 29276886
DOI 10.1021/acsami.7b13130
Protein Name peptide 1-2
Ice crystal morphology Fig.2 (a) Optical microscopic images of the ice crystal morphologies grown in pure water and the solutions of peptides 1-1, 1-2, and 1-3. (b) Optical images of the ice crystal grown in PBS buffer and peptide solutions. The scale bar is 100 μm.
Ice Recrystallization Inhibition
PMID 29276886
DOI 10.1021/acsami.7b13130
Protein Name peptide 1-2
Ice Recrystallization Inhibition Fig.2.B Optical images of the ice crystal grown in PBS buffer and peptide solutions. The scale bar is 100 μm.
Ice Grow Rate
PMID 40358480
DOI 10.1021/jacs.4c18537
Protein Name Peptide 93
Ice Grow Rate Fig.4 Ability of AFPTs to inhibit ice growth. (a) Growth processes of single ice crystals in H2O, E-1, E-2, E-3, E-4, and E-5 aqueous dispersions. (b) Quantitative assessment of ice growth rates in different aqueous dispersions. (c) Structures of AGPS, E-6, and E-7. (d) Growth processes of single ice crystals in AGPS, E-6, and E-7 aqueous dispersions. (e) Ice growth rates of >100 AFPTs aqueous solutions. Scale bar: 100 μm.
Brief description
PMID: 29276886
DOI: 10.1021/acsami.7b13130
1. This study designs three 12-amino acid α-helical antifreeze peptides inspired by type I AFP to investigate their antifreeze properties.
2. Different antifreeze peptides have different effects on ice crystal morphology. Peptides 1-1 and 1-2 can modify the ice crystal morphology, while peptide 1-3 has no such effect.
3. The ice recrystallization inhibition activities of antifreeze peptides are different. Peptide 1-2 has this activity, while peptides 1-1 and 1-3 do not.
PMID: 40358480
DOI: 10.1021/jacs.4c18537
1. Glutamic acid (E) is identified as the strongest ice-binding site (IBS)​, with 4-fold higher binding energy than natural IBSs like threonine (T), enabling significant enhancement of antifreeze activity in designed peptides.
2. ​A "Site to Distance" principle is established for de novo design of AFPTs, involving incorporation of E residues and tuning distances between IBSs to match ice crystal lattices (e.g., 6.4 Å for 1.5 lattices on the prism plane), resulting in superior ice growth inhibition.
3. Designed AFPTs (e.g., E-2 and triE) exhibit exceptional ice growth inhibition and thermal hysteresis (TH) activity, outperforming over 100 natural or previously reported AFPTs, with applications in cell cryopreservation showing high post-thaw viability.

AFP011009082

Mutation A7F,13_37del
Sequence
Ice crystal morphology
PMID 29276886
DOI 10.1021/acsami.7b13130
Protein Name peptide 1-3
Ice crystal morphology Fig.2 (a) Optical microscopic images of the ice crystal morphologies grown in pure water and the solutions of peptides 1-1, 1-2, and 1-3. (b) Optical images of the ice crystal grown in PBS buffer and peptide solutions. The scale bar is 100 μm.
Ice Recrystallization Inhibition
PMID 29276886
DOI 10.1021/acsami.7b13130
Protein Name peptide 1-3
Ice Recrystallization Inhibition "However, the peptides 1-1 and 1-3 do not exhibit IRI activity."
Ice Grow Rate
PMID 40358480
DOI 10.1021/jacs.4c18537
Protein Name Peptide 94
Ice Grow Rate Fig.4 Ability of AFPTs to inhibit ice growth. (a) Growth processes of single ice crystals in H2O, E-1, E-2, E-3, E-4, and E-5 aqueous dispersions. (b) Quantitative assessment of ice growth rates in different aqueous dispersions. (c) Structures of AGPS, E-6, and E-7. (d) Growth processes of single ice crystals in AGPS, E-6, and E-7 aqueous dispersions. (e) Ice growth rates of >100 AFPTs aqueous solutions. Scale bar: 100 μm.
Brief description
PMID: 29276886
DOI: 10.1021/acsami.7b13130
1. This study designs three 12-amino acid α-helical antifreeze peptides inspired by type I AFP to investigate their antifreeze properties.
2. Different antifreeze peptides have different effects on ice crystal morphology. Peptides 1-1 and 1-2 can modify the ice crystal morphology, while peptide 1-3 has no such effect.
3. The ice recrystallization inhibition activities of antifreeze peptides are different. Peptide 1-2 has this activity, while peptides 1-1 and 1-3 do not.
PMID: 40358480
DOI: 10.1021/jacs.4c18537
1. Glutamic acid (E) is identified as the strongest ice-binding site (IBS)​, with 4-fold higher binding energy than natural IBSs like threonine (T), enabling significant enhancement of antifreeze activity in designed peptides.
2. ​A "Site to Distance" principle is established for de novo design of AFPTs, involving incorporation of E residues and tuning distances between IBSs to match ice crystal lattices (e.g., 6.4 Å for 1.5 lattices on the prism plane), resulting in superior ice growth inhibition.
3. Designed AFPTs (e.g., E-2 and triE) exhibit exceptional ice growth inhibition and thermal hysteresis (TH) activity, outperforming over 100 natural or previously reported AFPTs, with applications in cell cryopreservation showing high post-thaw viability.

AFP011009083

Mutation Designed
Sequence
Ice crystal morphology
PMID 10437807
DOI 10.1016/S0014-5793(99)00906-0
Protein Name artificial AFP LKAAK
Ice crystal morphology Fig. 5. Photographs showing the effects of LKAAK and AKAAK on ice crystal morphology. (A) An ice crystal grown in a 23 mM LKAAK solution within the hysteresis gap, the c/a ratio is 5.7. (B) The same crystal as (A) showing a hexagonal trapezohedral shape after the temperature was lowered below the non-equilibrium freezing point, the c/a ratio has increased to 8.5. (C) An ice crystal grown in a 31 mM AKAAK within the thermal hysteresis gap, the c/a ratio is 5.4. (D) The same crystal as (C) after the temperature was lowered below the non-equilibrium freezing point, the c/a ratio is 8.5.
Thermal Hysteresis
PMID 10437807
DOI 10.1016/S0014-5793(99)00906-0
Protein Name artificial AFP LKAAK
Thermal Hysteresis Fig. 3. Antifreeze activity (thermal hysteresis) as a function of the concentration. Assay solutions contained 0.1 M ammonium bicarbonate buffer (pH ~8). Activity is de¢ned as the di°erence between the equilibrium melting point of ice and the non-equilibrium freezing point.
Brief description
PMID: 10437807
DOI: 10.1016/S0014-5793(99)00906-0
1. Lysine residues must be regularly spaced (KAAK motif) on the α-helix to confer antifreeze activity; irregular spacing abolishes activity.
2. Leu residues are dispensable for activity (AKAAK vs LKAAK), suggesting hydrophobic side chains are non-essential in this artificial system.
3. Antifreeze activity of LKAAK is pH-independent (pH 2–13), implying lysine-ice interaction persists regardless of protonation state.

AFP011009084

Mutation Designed
Sequence
Ice crystal morphology
PMID 10437807
DOI 10.1016/S0014-5793(99)00906-0
Protein Name artificial AFP AKAAk
Ice crystal morphology Fig. 5. Photographs showing the effects of LKAAK and AKAAK on ice crystal morphology. (A) An ice crystal grown in a 23 mM LKAAK solution within the hysteresis gap, the c/a ratio is 5.7. (B) The same crystal as (A) showing a hexagonal trapezohedral shape after the temperature was lowered below the non-equilibrium freezing point, the c/a ratio has increased to 8.5. (C) An ice crystal grown in a 31 mM AKAAK within the thermal hysteresis gap, the c/a ratio is 5.4. (D) The same crystal as (C) after the temperature was lowered below the non-equilibrium freezing point, the c/a ratio is 8.5.
Thermal Hysteresis
PMID 10437807
DOI 10.1016/S0014-5793(99)00906-0
Protein Name artificial AFP AKAAk
Thermal Hysteresis Fig. 3. Antifreeze activity (thermal hysteresis) as a function of the concentration. Assay solutions contained 0.1 M ammonium bicarbonate buffer (pH ~8). Activity is de¢ned as the di°erence between the equilibrium melting point of ice and the non-equilibrium freezing point.
Brief description
PMID: 10437807
DOI: 10.1016/S0014-5793(99)00906-0
1. Lysine residues must be regularly spaced (KAAK motif) on the α-helix to confer antifreeze activity; irregular spacing abolishes activity.
2. Leu residues are dispensable for activity (AKAAK vs LKAAK), suggesting hydrophobic side chains are non-essential in this artificial system.
3. Antifreeze activity of LKAAK is pH-independent (pH 2–13), implying lysine-ice interaction persists regardless of protonation state.

AFP011009085

Mutation Designed
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P1
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P1
Thermal Hysteresis "As in P1-P5, as the temperature is lowered, ice crystals continue to grow even after the WF double pyramid is developed, and there is no measurable freezing hysteresis."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P1
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Brief description
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.

AFP011009086

Mutation Designed
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P2
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P2
Thermal Hysteresis "As in P1-P5, as the temperature is lowered, ice crystals continue to grow even after the WF double pyramid is developed, and there is no measurable freezing hysteresis."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P2
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Brief description
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.

AFP011009087

Mutation Designed
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P3
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P3
Thermal Hysteresis "As in P1-P5, as the temperature is lowered, ice crystals continue to grow even after the WF double pyramid is developed, and there is no measurable freezing hysteresis."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P3
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Brief description
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.

AFP011009088

Mutation Designed
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P4
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P4
Thermal Hysteresis "As in P1-P5, as the temperature is lowered, ice crystals continue to grow even after the WF double pyramid is developed, and there is no measurable freezing hysteresis."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P4
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Brief description
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.

AFP011009089

Mutation Designed
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P5
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P5
Thermal Hysteresis "As in P1-P5, as the temperature is lowered, ice crystals continue to grow even after the WF double pyramid is developed, and there is no measurable freezing hysteresis."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P5
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Brief description
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.

AFP011009090

Mutation Designed
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P6
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P6
Thermal Hysteresis "As in P1-P5, as the temperature is lowered, ice crystals continue to grow even after the WF double pyramid is developed, and there is no measurable freezing hysteresis."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P6
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Brief description
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.

AFP011009091

Mutation Designed
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P7
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P7
Thermal Hysteresis "As the temperature is lowered, ice crystals continue to grow even after the hexagonal bipyramidal morphology … is completed, and there is no measurable freezing hysteresis."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P7
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Brief description
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.

AFP011009092

Mutation Designed
Sequence
Ice crystal morphology
PMID N/A
DOI 10.1021/cg8003855
Protein Name P8
Ice crystal morphology Fig.3 Inhibited ice crystal morphologies in the presence of P1-P9. Scale bars indicate 0.01 mm.
Thermal Hysteresis
PMID N/A
DOI 10.1021/cg8003855
Protein Name P8
Thermal Hysteresis "P8 is the first design in our series P1-P9 that exhibits the “apparent” freezing hysteresis, also reported for ATAAN."
Ice Hemisphere Etching
PMID N/A
DOI 10.1021/cg8003855
Protein Name P8
Ice Hemisphere Etching Fig.4 Initial (I) and scrape (S) etch patterns of ice hemispheres grown from the solutions of peptides P1-P9. The ice orientations are as in Figure 3 of ref 4, where tracings of the etch patterns for solutions of WF and SS are also shown.
Brief description
DOI: 10.1021/cg8003855
1. Nonpolar functional groups play a crucial role in the recognition and adsorption of type I AFPs to specific sites on the ice surface.
2. Experimental results show that the adsorption of antifreeze proteins is orientation-dependent. For example, winter flounder (WF) type AFPs primarily adsorb on the bipyramidal {2 0 1} faces of ice, while short-horn sculpin (SS) type AFPs adsorb on the secondary prismatic {2 1_ 0} faces. This orientation dependence is critical for understanding how AFPs inhibit ice crystal growth.
3. The function of AFPs relies on the participation of both polar and nonpolar residues in the recognition and binding to the ice surface.