Structural basis of coagulation factor V recognition for cleavage by RVV-V

Abstract Russell’s viper venom factor V (FV) activator (RVV-V) is a thrombin-like proteinase that specifically cleaves the Arg1545–Ser1546 bond of FV. Here we present the crystal structure of RVV-V in complex with the FV14 peptide (residues 1533–1546 of human FV) determined at 1.8 A resolution. The structure reveals multiple interactions between RVV-V and the seven residues, Ile1539 (P 7 )–Arg1545 (P 1 ), of the cleaved substrate. Comparison with substrate-free structures reveals conformational changes of the RVV-V loops upon substrate binding, suggesting that the multiple interactions are mediated by an induced-fit mechanism. The results provide an explanation for the narrow specificity of RVV-V.