The dimeric structure of factor XI and zymogen activation.

摘要: Factor XI (fXI) is a homodimeric zymogen that converted to protease with 1 (1/2-fXIa) or 2 (fXIa) active subunits by factor XIIa (fXIIa) thrombin. It has been proposed the dimeric structure required for normal fXI activation. Consistent this premise, monomers do not reconstitute fXI-deficient mice in fXIIa-dependent thrombosis model. FXI activation fXIIa thrombin slow reaction can be accelerated polyanions. Phosphate polymers released from platelets (poly-P) enhance and promote autoactivation. Poly-P increased initial rates of 30- 3000-fold thrombin, respectively. were activated more slowly than dimers presence poly-P. However, defect was observed when activating protease, nor during The data suggest activate different mechanisms. FXIIa may through trans-activation mechanism which binds subunit dimer, while other subunit. For autoactivation, support cis-activation activates same