[From structure to function: new developments in the interaction of coagulation factor Ⅴ with tissue factor pathway inhibitor α].

Abstract

The interaction between coagulation factor Ⅴ (FⅤ) and tissue factor pathway inhibitor alpha (TFPIα) is a central regulator of hemostatic balance. The acidic region (AR2) of the FⅤ B domain interacts with either its basic region (BR) or the basic C-terminal tail of TFPIα, modulating FⅤ activity. Recent cryo-electron microscopy studies have resolved the high-resolution structures of FⅤ-short and full-length FⅤ, revealing that AR2 forms a negatively charged hydrophobic platform that mediates BR or TFPIα binding. These insights confirm the BR-AR2 interaction as crucial for maintaining FⅤ in its inactive state and clarify the molecular basis of FⅤ-related disorders, highlighting the FⅤ-TFPIα interface as a promising therapeutic target for bleeding and thrombotic diseases.