Abstract
Vitamin K-dependent coagulation plasma proteins possess from 9–12 residues of γ-carboxyglutamic acid (Gla) distributed over a ca. 45 amino acid peptide sequence, i.e., the Gla domain, which encompasses the NH2-terminal region. In addition, epidermal growth factor (EGF) homology units present in many of these same proteins contain β-hydroxyaspartate (Hya) residues, which is a modi? cation decoupled from γ-carboxylation (1). The function of Gla residues in these proteins, viz., prothrombin, coagulation factors VII, IX, and X, along with anticoagulant protein C and protein S, is to coordinate Ca2+. This results in a large conformational alteration in the proteins or peptides, which allows adsorption to membrane phospholipids (PL), an event that is critical is to their proper functions in the blood coagulation system (2,3). Less certain is the role of Hya in EGF domains, but it has been proposed that modi? cation at this residue may negatively regulate fucosylation of these regions (4). In several proteins, these modules also interact with Ca2+, but it has been shown that while the particular aspartate containing the β-OH group is critical to that interaction, β-hydroxylation of that Asp residue is not.
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Castellino, F.J., Ploplis, V.A., Zhang, L. (2002). γ-Glutamate and p-Hydroxyaspartate in Proteins. In: Kannicht, C. (eds) Posttranslational Modifications of Proteins. Methods in Molecular Biology™, vol 194. Humana Press. https://doi.org/10.1385/1-59259-181-7:259
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DOI: https://doi.org/10.1385/1-59259-181-7:259
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