Interactions of vitamin K-dependent proteins with calcium ions and phospholipid membranes

The calcium-dependent interaction of vitamin K-dependent proteins with membranes is a complex process that minimally consists of 1) calcium binding to the protein and an essential calcium-dependent protein transition, 2) an essential calcium-membrane interaction, and 3) formation of the protein-membrane complex. Below about 5 mM calcium, the protein-membrane complex binds more calcium than the sum of the components but at higher concentrations protein-membrane binding is not accompanied by additional cation binding. These protein-menbrane interactions function in blood coagulation by increasing the binding affinity of the active site. The increased affinity results from the additive effects of protein-membrane (e.g., prothrombin-, factor Xa- and factor V-membrane) interactions and protein-protein (e.g., factor Xa- factor V and prothrombin-factor V) interactions. The prothrombinase complex can be viewed kinetically as a dissociable three-component enzyme (factor Xa, factor V, and phospholipid) acting on the soluble substrate, prothrombin.