Participation of the factor V molecule in the hemostatic process.

Four stages of the participation of the factor V molecule in the hemostatic process are illustrated in in cartoon form. (A) The factor V molecule is presented with the activation peptide “B domain” illustrated as a loop structure which connects the heavy (A₁A₂) and light chain (A₃C₁C₂) domains of the factor Va molecule. The single chain factor V interacts with membranes through its carboxyl terminal region. (B) Factor V is activated to Factor Va by thrombin (IIa), which excises the B domain, leaving the noncovalently associated light and heavy chains of the factor Va molecule. (C) The membrane-bound factor Va molecule binds factor Xa through regions of both the light and heavy chains. These interactions together with factor Xa membrane binding provide the tightly associated enzymatic complex (prothrombinase) which converts prothrombin (II) to thrombin (IIa). (D) Activated protein C (APC) cleaves at 3 sites of the heavy chain of the factor Va molecule, resulting in the dissociation of the A₂ domain as 2 fragments, A₂N and A₂C. The resulting product (factor Vai), composed of the A₁ domain noncovalently associated with the membrane-bound light chain, binds APC but will no longer function efficiently in generating thrombin.