Three-dimensional model of coagulation factor Va bound to activated protein C

A complete molecular model of blood coagulation factor Va (FVa) bound to an ticoagulant activated protein C (APC) and to a phospholipid membrane was co nstructed. The three homologous A domains and the two homologous C domains of FVA were modeled based on the X-ray crystallographic structures of cerul oplasmin and C2 domain of factor V, respectively. The final arrangement of the five domains in the complete FVa model bound to a membrane incorporated extensive published experimental data. FVa binds the phospholipid membrane through its C2 domain while the A-domain trimer is located from 40 through 100 Angstrom above the membrane plane. From our model we infer a probable role for metal ions at the interface between FVa light and heavy chains, pr ovide an explanation for the slower APC cleavage at Arg306 relative to Arg5 06, and predict specific interactions between positively and negatively cha rged exosites in APC and FVa, respectively.