Molecular dynamics simulations and functional characterization of the interactions of the PAR2 ectodomain with factor VIIa.

ABSTRACT: Signaling of the tissue factor-FVIIa complex regulates angiogenesis, tumor growth, and inflammation. TF-FVIIa triggers cell signaling events by cleavage of protease activated receptor (PAR2) at the Arg36-Ser37 scissile bond. The recognition of PAR2 by the FVIIa protease domain is poorly understood. We perform molecular modeling and dynamics simulations to derive the PAR2-FVIIa interactions. Docking of the PAR2 Arg36-Ser37 scissile bond to the S1 site and subsequent molecular dynamics leads to interactions of the PAR2 ectodomain with P and P' sites of the FVIIa catalytic cleft as well as to electrostatic interactions between a stably folded region of PAR2 and a cluster of basic residues remote from the catalytic cleft of FVIIa. To address the functional significance of this interaction for

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC2913976 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature