Atomistic Mechanism of Lipid Membrane Binding for Blood Coagulation Factor VIII with Molecular Dynamics Simulations on a Microsecond Time Scale.

ABSTRACT: During the blood coagulation cascade, coagulation factor VIII (FVIII) is activated by thrombin to form activated factor VIII (FVIIIa). FVIIIa associates with platelet surfaces at the site of vascular damage to form an intrinsic tenase complex with activated factor IX. A working model for FVIII membrane binding involves the association of positively charged FVIII residues with negatively charged lipid headgroups and the burial of hydrophobic residues into the membrane interior. Currently, the atomic details of the FVIII lipid binding interactions and membrane orientation are lacking. This study reports residue-specific FVIII C domain interactions with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS) in atomistic detail. Cont

SUBMITTER: Avery NG 

PROVIDER: S-EPMC11808648 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature