Tissue factor mutated at the allosteric Cys186-Cys209 disulfide bond is severely impaired in decrypted procoagulant activity.

摘要

Tissue factor (TF) is the cellular trigger of extrinsic coagulation and a signaling coreceptor for protease-activated receptor 2 (PAR2), Procoagulant activity of TF-factor (F) VIIa saturates at subnanomo-lar concentrations of FVIIa, whereas the TF-FVIIa binary complex signals efficiently at approximately 10nM FVIIa, the plasma concentration of zymogen FVII. Mutation of the TF allosteric Cys~(186)-Cys~(209) disulfide bond abolishes signaling of the procoagulant TF-FVIIa-FXa coagulation initiation complex, while preserving signaling activity as a binary TF-FVIIa complex.