The vitamin K-dependent coagulation plasma proteins possess from 9 to 12 residues of γ-carboxyglutamic acid (Gla) distributed in an approx 40 amino acid peptide sequence, that is, the Gla domain, which encompasses the N-terminal region. In the presence of Ca2+ and negatively charged phospholipids (PLs), the Gla domain functions as the site of protein attachment to membranes. Strong evidence exists that the adsorption of these proteins to membranes is driven by a Ca2+ -mediated bridging interaction between negatively charged PL (e.g., phosphatidylserine) and the Gla residues of proteins (for a review,seeref.1 ). More recent studies demonstrated that adsorption to PL membranes of Glacontaining coagulation proteins, such as VII, factor IXa, factor X, prothrombin, and protein C (PC), also possessed a significant hydrophobic determinant (2 –6 ). Adsorption of the Gla-containing coagulation proteins to membranes is critical to proper function of the blood coagulation system.
