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

FEBS Lett. 2011 Oct 3;585(19):3020-5. doi: 10.1016/j.febslet.2011.08.022. Epub 2011 Aug 23.

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 1.8Å 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Factor V / chemistry*
  • Factor V / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation*
  • Sequence Alignment
  • Serine Endopeptidases / chemistry*
  • Serine Endopeptidases / metabolism*
  • Substrate Specificity

Substances

  • Factor V
  • Serine Endopeptidases
  • snake venom factor V activator