‘Antifreeze’ glycoproteins from polar fish

• Published in: European Journal of Biochemistry
• Main Authors: Harding, Margaret M., Anderberg, Pia I., Haymet, A. D. J.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2003
• Subjects: Antarctic; Arctic; Antarc*; Arctic cod
• Online Access: http://dx.doi.org/10.1046/j.1432-1033.2003.03488.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1432-1033.2003.03488.x; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1432-1033.2003.03488.x

Antifreeze glycoproteins (AFGPs) constitute the major fraction of protein in the blood serum of Antarctic notothenioids and Arctic cod. Each AFGP consists of a varying number of repeating units of (Ala‐Ala‐Thr) n , with minor sequence variations, and the disaccharide β‐ d ‐galactosyl‐(1→3)‐α‐ N ‐acetyl‐ d ‐galactosamine joined as a glycoside to the hydroxyl oxygen of the Thr residues. These compounds allow the fish to survive in subzero ice‐laden polar oceans by kinetically depressing the temperature at which ice grows in a noncolligative manner. In contrast to the more widely studied antifreeze proteins, little is known about the mechanism of ice growth inhibition by AFGPs, and there is no definitive model that explains their properties. This review summarizes the structural and physical properties of AFGPs and advances in the last decade that now provide opportunities for further research in this field. High field NMR spectroscopy and molecular dynamics studies have shown that AFGPs are largely unstructured in aqueous solution. While standard carbohydrate degradation studies confirm the requirement of some of the sugar hydroxyls for antifreeze activity, the importance of following structural elements has not been established: (a) the number of hydroxyls required, (b) the stereochemistry of the sugar hydroxyls (i.e. the requirement of galactose as the sugar), (c) the acetamido group on the first galactose sugar, (d) the stereochemistry of the β‐glycosidic linkage between the two sugars and the α‐glycosidic linkage to Thr, (e) the requirement of a disaccharide for activity, and (f) the Ala and Thr residues in the polypeptide backbone. The recent successful synthesis of small AFGPs using solution methods and solid‐phase chemistry provides the opportunity to perform key structure‐activity studies that would clarify the important residues and functional groups required for activity. Genetic studies have shown that the AFGPs present in the two geographically and phylogenetically distinct Antarctic notothenioids and ...