Effect of Ca ²⁺ on the Structure of Vitamin K-Dependent Coagulation Factors

Coagulation factors VII, IX, X, and protein C contain an N-terminal module with 9-12 gamma-carboxyglutamic acid (Gla) residues. It is followed by two modules that are homologous to the epidermal growth factor (EGF) and a C-terminal serine protease module. Upon calcium binding to the Gla module the side chains of three hydrophobic residues are exposed in a manner indicating that they interact with biological membranes. The calcium-binding site in the first EGF-like module appears to be required for proper orientation of the Gla and EGF-like modules relative to each other. A single calcium-binding site is also present in the serine protease module. The properties of these calcium-binding sites are briefly reviewed.