Figure 1
From: Modeling of human factor Va inactivation by activated protein C
Schematic Representation of Factor Va and the Mechanism of the APC-Generated Partially Proteolyzed Species. Human factor Va (FVa), consisting of the non-covalently associated 105 kDa heavy chain (FVaHC) and 74/72 kDa light chain (two carbohydrate variants) (FVaLC), has maximal cofactor activity in the prothrombinase complex. FVa contains three APC cleavage sites: Arg306, Arg506, and Arg679; cleavage at Arg679 plays a minimal role in altering cofactor activity and so will not be considered further. APC cleaves FVa in a random, non-sequential manner at Arg306 and Arg506 leading to the formation of partially proteolyzed species (FVai306 and FVai506, respectively). FVai306 and FVai506 are subsequently proteolyzed by APC at Arg506 or Arg306, respectively, to generate the FVai306/506 species. Prothrombinase activity is possible even when the FVaHC has been proteolyzed at both sites as long as the heavy chain fragments remain associated with each other and the FVaLC. The partially active FVai306 and FVai306/506 species lose full activity with the spontaneous dissociation of either the FVa307-679/709 or FVa307-506FVa507-679/709 fragments, respectively. Fragments shaded in black are recognized by the monoclonal antibody (αHFV#17) and their apparent (SDS-PAGE) molecular weights are indicated.