Membrane-bound model of the ternary complex between factor VIIa/tissue factor and factor X.

ABSTRACT:

Abstract

Formation of the extrinsic complex (EC) on cell surfaces is the event that triggers the coagulation cascade. Tissue factor (TF) and factor VIIa (FVIIa) form the EC together with FX on phosphatidylserine-containing membranes, leading to FX activation by TF:FVIIa. This lipid dependence has made experimental characterization of the EC structure challenging. Using a novel computational methodology combining rigid-body protein-protein docking and extensive nonequilibrium molecular dynamics simulations in the explicit presence of a membrane, we developed, to our knowledge, the first atomic-level model of the EC, taking full account of the role of the membrane. Rigid-body docking generated 1 000 000 protein-only structures that predict the binding of key EC domains. Residue-resid

SUBMITTER: Muller MP 

PROVIDER: S-EPMC11869871 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature