antifreeze proteins


Summary: Proteins that bind to ice and modify the growth of ice crystals. They perform a cryoprotective role in a variety of organisms.

Top Publications

  1. Scotter A, Marshall C, Graham L, Gilbert J, Garnham C, Davies P. The basis for hyperactivity of antifreeze proteins. Cryobiology. 2006;53:229-39 pubmed
    b>Antifreeze proteins (AFPs) bind to the surface of ice crystals and lower the non-equilibrium freezing temperature of the icy solution below its melting point...
  2. Atici O, Nalbantoglu B. Antifreeze proteins in higher plants. Phytochemistry. 2003;64:1187-96 pubmed
    Overwintering plants produce antifreeze proteins (AFPs) having the ability to adsorb onto the surface of ice crystals and modify their growth...
  3. Kondo H, Hanada Y, Sugimoto H, Hoshino T, Garnham C, Davies P, et al. Ice-binding site of snow mold fungus antifreeze protein deviates from structural regularity and high conservation. Proc Natl Acad Sci U S A. 2012;109:9360-5 pubmed publisher
    b>Antifreeze proteins (AFPs) are found in organisms ranging from fish to bacteria, where they serve different functions to facilitate survival of their host...
  4. Nagel L, Plattner C, Budke C, Majer Z, Devries A, Berkemeier T, et al. Synthesis and characterization of natural and modified antifreeze glycopeptides: glycosylated foldamers. Amino Acids. 2011;41:719-32 pubmed publisher
    ..Furthermore, the foldamers were analysed microphysically according to their inhibiting effect on ice recrystallization and influence on the crystal habit. ..
  5. Duman J, Li N, Verleye D, Goetz F, Wu D, Andorfer C, et al. Molecular characterization and sequencing of antifreeze proteins from larvae of the beetle Dendroides canadensis. J Comp Physiol B. 1998;168:225-32 pubmed
    The deduced amino acid sequences of antifreeze proteins (AFPs) from larvae of the beetle Dendroides canadensis were determined from both complementary DNAs (cDNAs) and from peptide sequencing...
  6. Xiao N, Suzuki K, Nishimiya Y, Kondo H, Miura A, Tsuda S, et al. Comparison of functional properties of two fungal antifreeze proteins from Antarctomyces psychrotrophicus and Typhula ishikariensis. FEBS J. 2010;277:394-403 pubmed publisher
    b>Antifreeze proteins are structurally diverse polypeptides that have thermal hysteresis activity and have been discovered in many cold-adapted organisms...
  7. Capicciotti C, Trant J, Leclère M, Ben R. Synthesis of C-linked triazole-containing AFGP analogues and their ability to inhibit ice recrystallization. Bioconjug Chem. 2011;22:605-16 pubmed publisher
    ..These results suggest that, while the triazole group is a structural mimetic of an amide bond, the amide bond in C-AFGP analogue 3 is an essential structural feature necessary for potent IRI activity. ..
  8. Leclère M, Kwok B, Wu L, Allan D, Ben R. C-linked antifreeze glycoprotein (C-AFGP) analogues as novel cryoprotectants. Bioconjug Chem. 2011;22:1804-10 pubmed publisher
    ..Our results indicate that a 1-1.5 mg/mL (0.5-0.8 mM) solution of C-AFGP 1 is an excellent alternative to a 2.5% DMSO solution for the cryopreservation of human embryonic liver cells. ..
  9. Muldrew K, Rewcastle J, Donnelly B, Saliken J, Liang S, Goldie S, et al. Flounder antifreeze peptides increase the efficacy of cryosurgery. Cryobiology. 2001;42:182-9 pubmed
    ..However, a double-freeze procedure with antifreeze protein present was found to give significantly better ablation than a double-freeze without AFP or a single-freeze with or without AFP. ..

More Information


  1. Bagis H, Akkoç T, Tasş A, Aktoprakligil D. Cryogenic effect of antifreeze protein on transgenic mouse ovaries and the production of live offspring by orthotopic transplantation of cryopreserved mouse ovaries. Mol Reprod Dev. 2008;75:608-13 pubmed
    ..These results demonstrate that a normal reproductive lifespan can be restored by orthotopic transplantation of AFP transgenic-vitrified ovary. ..
  2. Liu S, Wang W, Moos E, Jackman J, Mealing G, Monette R, et al. In vitro studies of antifreeze glycoprotein (AFGP) and a C-linked AFGP analogue. Biomacromolecules. 2007;8:1456-62 pubmed
    ..Although the results from these studies limit the human applications of native AFGP, they illustrate the benefits of developing functional C-linked AFGP analogues for various medical, commercial and industrial applications. ..
  3. Driedzic W, Ewart K. Control of glycerol production by rainbow smelt (Osmerus mordax) to provide freeze resistance and allow foraging at low winter temperatures. Comp Biochem Physiol B Biochem Mol Biol. 2004;139:347-57 pubmed
    ..Overall, the phenomenon of glycerol production by rainbow smelt reveals an elegant connection of biochemistry to ecology that allows this species to exploit an otherwise unavailable food resource...
  4. Garnham C, Campbell R, Davies P. Anchored clathrate waters bind antifreeze proteins to ice. Proc Natl Acad Sci U S A. 2011;108:7363-7 pubmed publisher
    The mechanism by which antifreeze proteins (AFPs) irreversibly bind to ice has not yet been resolved. The ice-binding site of an AFP is relatively hydrophobic, but also contains many potential hydrogen bond donors/acceptors...
  5. Matsumoto S, Matsusita M, Morita T, Kamachi H, Tsukiyama S, Furukawa Y, et al. Effects of synthetic antifreeze glycoprotein analogue on islet cell survival and function during cryopreservation. Cryobiology. 2006;52:90-8 pubmed
    ..In conclusion, the attenuation of ice crystallization by syAFGP improves islet survival and function following cryopreservation and thawing. ..
  6. Eniade A, Murphy A, Landreau G, Ben R. A general synthesis of structurally diverse building blocks for preparing analogues of C-linked antifreeze glycoproteins. Bioconjug Chem. 2001;12:817-23 pubmed
    ..All reactions are general in nature and accommodate structural variation in the carbohydrate moiety, polypeptide backbone, and amino acid side chain. ..
  7. Nagel L, Budke C, Erdmann R, Dreyer A, Wennemers H, Koop T, et al. Influence of sequential modifications and carbohydrate variations in synthetic AFGP analogues on conformation and antifreeze activity. Chemistry. 2012;18:12783-93 pubmed publisher
    ..The conformations of all analogues were examined by circular dichroism (CD). In addition, microphysical analysis was performed to provide information on their inhibitory effect on ice recrystallization. ..
  8. Venketesh S, Dayananda C. Properties, potentials, and prospects of antifreeze proteins. Crit Rev Biotechnol. 2008;28:57-82 pubmed
    b>Antifreeze proteins (AFPs) are a group of proteins that protect organisms from deep freezing temperatures and are expressed in vertebrates, invertebrates, plants, bacteria, and fungi...
  9. Pertaya N, Marshall C, DiPrinzio C, Wilen L, Thomson E, Wettlaufer J, et al. Fluorescence microscopy evidence for quasi-permanent attachment of antifreeze proteins to ice surfaces. Biophys J. 2007;92:3663-73 pubmed
    Many organisms are protected from freezing by the presence of extracellular antifreeze proteins (AFPs), which bind to ice, modify its morphology, and prevent its further growth...
  10. Yang Z, Zhou Y, Liu K, Cheng Y, Liu R, Chen G, et al. Computational study on the function of water within a beta-helix antifreeze protein dimer and in the process of ice-protein binding. Biophys J. 2003;85:2599-605 pubmed
    b>Antifreeze proteins (AFPs) help many organisms protect themselves from freezing in subzero temperatures. The most active AFPs found to date are those from insects, which possess exceptionally regular beta-helical structures...
  11. Hew C, Poon R, Xiong F, Gauthier S, Shears M, King M, et al. Liver-specific and seasonal expression of transgenic Atlantic salmon harboring the winter flounder antifreeze protein gene. Transgenic Res. 1999;8:405-14 pubmed
    ..This study had demonstrated a tissue-specific and stable expression of the antifreeze protein transgene in the F3 generation of the transgenic salmon 1469 line. ..
  12. Graham L, Davies P. Glycine-rich antifreeze proteins from snow fleas. Science. 2005;310:461 pubmed
    We purified antifreeze proteins from winter-active snow fleas, Hypogastrura harveyi. These 6.5- and 15...
  13. Griffith M, Yaish M. Antifreeze proteins in overwintering plants: a tale of two activities. Trends Plant Sci. 2004;9:399-405 pubmed
    b>Antifreeze proteins are found in a wide range of overwintering plants where they inhibit the growth and recrystallization of ice that forms in intercellular spaces...
  14. Garner J, Harding M. Design and synthesis of alpha-helical peptides and mimetics. Org Biomol Chem. 2007;5:3577-85 pubmed
    ..Examples where synthetic compounds have delivered promising biological results will be highlighted as well as opportunities for the design of mimetics of the type I alpha-helical antifreeze proteins.
  15. Wang L, Duman J. A thaumatin-like protein from larvae of the beetle Dendroides canadensis enhances the activity of antifreeze proteins. Biochemistry. 2006;45:1278-84 pubmed
    The levels of thermal hysteresis (antifreeze activity) produced by purified antifreeze proteins (DAFPs) from the larvae of the beetle Dendroides canadensis at endogenous concentrations are lower than what are present in the hemolymph of ..
  16. Pentelute B, Gates Z, Tereshko V, Dashnau J, Vanderkooi J, Kossiakoff A, et al. X-ray structure of snow flea antifreeze protein determined by racemic crystallization of synthetic protein enantiomers. J Am Chem Soc. 2008;130:9695-701 pubmed publisher
    ..These results illustrate the utility of total chemical synthesis combined with racemic crystallization and X-ray crystallography for determining the unknown structure of a protein. ..
  17. Celik Y, Drori R, Pertaya Braun N, Altan A, Barton T, Bar Dolev M, et al. Microfluidic experiments reveal that antifreeze proteins bound to ice crystals suffice to prevent their growth. Proc Natl Acad Sci U S A. 2013;110:1309-14 pubmed publisher
    b>Antifreeze proteins (AFPs) are a subset of ice-binding proteins that control ice crystal growth...
  18. Fletcher G, Hew C, Davies P. Antifreeze proteins of teleost fishes. Annu Rev Physiol. 2001;63:359-90 pubmed
    ..They avoid freezing by producing small antifreeze proteins (AFPs) that adsorb to ice and halt its growth, thereby producing an additional non-colligative lowering of ..
  19. Lee J, Park A, Do H, Park K, Moh S, Chi Y, et al. Structural basis for antifreeze activity of ice-binding protein from arctic yeast. J Biol Chem. 2012;287:11460-8 pubmed publisher
    ..Although LeIBP has a common ?-helical fold similar to that of canonical hyperactive antifreeze proteins, the ice-binding site is more complex and does not have a simple ice-binding motif...
  20. Zhang D, Liu B, Feng D, He Y, Wang S, Wang H, et al. Significance of conservative asparagine residues in the thermal hysteresis activity of carrot antifreeze protein. Biochem J. 2004;377:589-95 pubmed
    ..We also found that its thermal hysteresis activity is directly correlated with the length of its asparagine-rich binding site, and hence with the size of its ice-binding face. ..
  21. Clark M, Worland M. How insects survive the cold: molecular mechanisms-a review. J Comp Physiol B. 2008;178:917-33 pubmed publisher
  22. Ewart K, Lin Q, Hew C. Structure, function and evolution of antifreeze proteins. Cell Mol Life Sci. 1999;55:271-83 pubmed
    b>Antifreeze proteins bind to ice crystals and modify their growth. These proteins show great diversity in structure, and they have been found in a variety of organisms...
  23. Duncker B, Gauthier S, Davies P. Cystine-rich fish antifreeze is produced as an active proprotein precursor in fall armyworm cells. Biochem Biophys Res Commun. 1994;203:1851-7 pubmed
  24. Bar M, Bar Ziv R, Scherf T, Fass D. Efficient production of a folded and functional, highly disulfide-bonded beta-helix antifreeze protein in bacteria. Protein Expr Purif. 2006;48:243-52 pubmed
  25. Nicodemus Johnson J, Silic S, Ghigliotti L, Pisano E, Cheng C. Assembly of the antifreeze glycoprotein/trypsinogen-like protease genomic locus in the Antarctic toothfish Dissostichus mawsoni (Norman). Genomics. 2011;98:194-201 pubmed publisher
    ..This study provided the data for fine resolution sequence analyses that would yield insight into the molecular mechanisms of notothenioid AFGP gene family evolution driven by Southern Ocean glaciation. ..
  26. Bennett V, Sformo T, Walters K, Tøien Ø, Jeannet K, Hochstrasser R, et al. Comparative overwintering physiology of Alaska and Indiana populations of the beetle Cucujus clavipes (Fabricius): roles of antifreeze proteins, polyols, dehydration and diapause. J Exp Biol. 2005;208:4467-77 pubmed
    ..2 and 0.5 mol l(-1), respectively). In addition, both populations produce antifreeze proteins. Interestingly, in the autumn both populations have the same approximate level of hemolymph thermal ..
  27. Nicodemus J, O Tousa J, Duman J. Expression of a beetle, Dendroides canadensis, antifreeze protein in Drosophila melanogaster. J Insect Physiol. 2006;52:888-96 pubmed
    ..Transgenic Drosophila were also able to live significantly longer than controls at 0 degrees C and 4 degrees C, indicating that DAFP-1 is able to increase cold tolerance at above freezing temperatures. ..
  28. Amir G, Rubinsky B, Kassif Y, Horowitz L, Smolinsky A, Lavee J. Preservation of myocyte structure and mitochondrial integrity in subzero cryopreservation of mammalian hearts for transplantation using antifreeze proteins--an electron microscopy study. Eur J Cardiothorac Surg. 2003;24:292-6; discussion 296-7 pubmed
    ..lowering the freezing temperature of their body fluids using a family of thermal hysteresis proteins (antifreeze proteins, AFPs) specific for each species...
  29. Pudney P, Buckley S, Sidebottom C, Twigg S, Sevilla M, Holt C, et al. The physico-chemical characterization of a boiling stable antifreeze protein from a perennial grass (Lolium perenne). Arch Biochem Biophys. 2003;410:238-45 pubmed
    ..Ice-binding studies of both glycosylated and nonglycosylated expressed forms indicate that it adsorbs to ice through the protein backbone. These results are discussed in light of the currently proposed mechanisms of AFP action. ..
  30. Koike M, Okamoto T, Tsuda S, Imai R. A novel plant defensin-like gene of winter wheat is specifically induced during cold acclimation. Biochem Biophys Res Commun. 2002;298:46-53 pubmed
    ..Collectively, these data suggested that Tad1 is induced in cold-acclimated winter wheat independent of major defense signaling(s) and is involved in low temperature-induced resistance to pathogens during winter hardening...
  31. Middleton A, Marshall C, Faucher F, Bar Dolev M, Braslavsky I, Campbell R, et al. Antifreeze protein from freeze-tolerant grass has a beta-roll fold with an irregularly structured ice-binding site. J Mol Biol. 2012;416:713-24 pubmed publisher
    ..IBPs) are also produced by freeze-avoiding organisms to halt the growth of ice and are better known as antifreeze proteins (AFPs)...
  32. Celik Y, Graham L, Mok Y, Bar M, Davies P, Braslavsky I. Superheating of ice crystals in antifreeze protein solutions. Proc Natl Acad Sci U S A. 2010;107:5423-8 pubmed publisher
    It has been argued that for antifreeze proteins (AFPs) to stop ice crystal growth, they must irreversibly bind to the ice surface...
  33. Sonnichsen F, DeLuca C, Davies P, Sykes B. Refined solution structure of type III antifreeze protein: hydrophobic groups may be involved in the energetics of the protein-ice interaction. Structure. 1996;4:1325-37 pubmed
    b>Antifreeze proteins are found in certain fish inhabiting polar sea water...
  34. Duman J, Bennett V, Sformo T, Hochstrasser R, Barnes B. Antifreeze proteins in Alaskan insects and spiders. J Insect Physiol. 2004;50:259-66 pubmed
    Prior to this study, antifreeze proteins (AFPs) had not been identified in terrestrial arthropods from the Arctic or anywhere in Alaska...
  35. Gibson M, Barker C, Spain S, Albertin L, Cameron N. Inhibition of ice crystal growth by synthetic glycopolymers: implications for the rational design of antifreeze glycoprotein mimics. Biomacromolecules. 2009;10:328-33 pubmed publisher
  36. Miller N, Williams G, Brimble M. Synthesis of fish antifreeze neoglycopeptides using microwave-assisted "click chemistry". Org Lett. 2009;11:2409-12 pubmed publisher
  37. Tam R, Rowley C, Petrov I, Zhang T, Afagh N, Woo T, et al. Solution conformation of C-linked antifreeze glycoprotein analogues and modulation of ice recrystallization. J Am Chem Soc. 2009;131:15745-53 pubmed publisher
    ..These results illustrate how subtle changes in conformation and carbohydrate orientation dramatically influence IRI activity in C-linked AFGP analogues. ..
  38. D Amico S, Collins T, Marx J, Feller G, Gerday C. Psychrophilic microorganisms: challenges for life. EMBO Rep. 2006;7:385-9 pubmed
    ..In this review, we discuss the current knowledge of these adaptations as gained from extensive biochemical and biophysical studies and also from genomics and proteomics. ..
  39. Middleton A, Brown A, Davies P, Walker V. Identification of the ice-binding face of a plant antifreeze protein. FEBS Lett. 2009;583:815-9 pubmed publisher
    ..Three mutations that clustered on the other flat surface lost up to 90% of their antifreeze activity and identify this beta-sheet as the ice-binding face. ..
  40. Smolin N, Daggett V. Formation of ice-like water structure on the surface of an antifreeze protein. J Phys Chem B. 2008;112:6193-202 pubmed publisher
    b>Antifreeze proteins (AFPs) are found in different species from polar, alpine, and subarctic regions where they serve to inhibit ice crystal growth by adsorption to ice surfaces...
  41. Garnham C, Gilbert J, Hartman C, Campbell R, Laybourn Parry J, Davies P. A Ca2+-dependent bacterial antifreeze protein domain has a novel beta-helical ice-binding fold. Biochem J. 2008;411:171-80 pubmed
    AFPs (antifreeze proteins) are produced by many organisms that inhabit ice-laden environments. They facilitate survival at sub-zero temperatures by binding to, and inhibiting, the growth of ice crystals in solution...
  42. Lewis J, Ewart K, Driedzic W. Freeze resistance in rainbow smelt (Osmerus mordax): seasonal pattern of glycerol and antifreeze protein levels and liver enzyme activity associated with glycerol production. Physiol Biochem Zool. 2004;77:415-22 pubmed
    ..smelt accumulate high levels of glycerol, which lower the freezing point via colligative means, and antifreeze proteins (AFP)...
  43. Gilbert J, Hill P, Dodd C, Laybourn Parry J. Demonstration of antifreeze protein activity in Antarctic lake bacteria. Microbiology. 2004;150:171-80 pubmed
    b>Antifreeze proteins (AFPs) are a structurally diverse group of proteins that have the ability to modify ice crystal structure and inhibit recrystallization of ice...
  44. Gallagher K, Sharp K. Analysis of thermal hysteresis protein hydration using the random network model. Biophys Chem. 2003;105:195-209 pubmed
    ..It is concluded that these two specific features of the hydration structure are important for this surface to recognize, and preferentially interact with nascent ice crystals forming in liquid water. ..
  45. Leinala E, Davies P, Doucet D, Tyshenko M, Walker V, Jia Z. A beta-helical antifreeze protein isoform with increased activity. Structural and functional insights. J Biol Chem. 2002;277:33349-52 pubmed
    ..Thus, the enhanced antifreeze activity of CfAFP-501 is directly correlated to the length of its beta-helical structure and hence the size of its ice-binding face. ..
  46. Crevel R, Fedyk J, Spurgeon M. Antifreeze proteins: characteristics, occurrence and human exposure. Food Chem Toxicol. 2002;40:899-903 pubmed
    b>Antifreeze proteins (AFPs), also known as ice structuring proteins, bind to and influence the growth of ice crystals...
  47. Fairley K, Westman B, Pham L, Haymet A, Harding M, Mackay J. Type I shorthorn sculpin antifreeze protein: recombinant synthesis, solution conformation, and ice growth inhibition studies. J Biol Chem. 2002;277:24073-80 pubmed
  48. Wu Y, Banoub J, Goddard S, Kao M, Fletcher G. Antifreeze glycoproteins: relationship between molecular weight, thermal hysteresis and the inhibition of leakage from liposomes during thermotropic phase transition. Comp Biochem Physiol B Biochem Mol Biol. 2001;128:265-73 pubmed
    ..It is hypothesized that AFGP prevent liposomes from leaking as they pass through the phase transition temperature by binding to the phospholipid membrane. ..
  49. Graham L, Walker V, Davies P. Developmental and environmental regulation of antifreeze proteins in the mealworm beetle Tenebrio molitor. Eur J Biochem. 2000;267:6452-8 pubmed
    ..As all environmental conditions that caused increased thermal hysteresis also inhibited growth, we postulate that developmental arrest is a primary factor in the regulation of T. molitor thermal hysteresis proteins...
  50. Jia Z, DeLuca C, Chao H, Davies P. Structural basis for the binding of a globular antifreeze protein to ice. Nature. 1996;384:285-8 pubmed
    b>Antifreeze proteins (AFPs) have the unique ability to adsorb to ice and inhibit its growth. Many organisms ranging from fish to bacteria use AFPs to retard freezing or lessen the damage incurred upon freezing and thawing...
  51. Graham L, Marshall C, Lin F, Campbell R, Davies P. Hyperactive antifreeze protein from fish contains multiple ice-binding sites. Biochemistry. 2008;47:2051-63 pubmed publisher
    b>Antifreeze proteins (AFPs) are produced to prevent freezing in many fish species that are exposed to icy seawater...
  52. Bayer Giraldi M, Uhlig C, John U, Mock T, Valentin K. Antifreeze proteins in polar sea ice diatoms: diversity and gene expression in the genus Fragilariopsis. Environ Microbiol. 2010;12:1041-52 pubmed publisher
    ..Here we show that antifreeze proteins (AFPs), involved in cold adaptation in several psychrophilic organisms, are widespread in the two polar ..
  53. Lin F, Graham L, Campbell R, Davies P. Structural modeling of snow flea antifreeze protein. Biophys J. 2007;92:1717-23 pubmed
    ..Like several other antifreeze proteins, this modeled protein is amphipathic with a putative hydrophobic ice-binding face.