Physical Sciences and Mathematics Commons^™

Structural Studies Of Complexes Of Blood Coagulation Factor Viii, Joseph S. Gish

WWU Graduate School Collection

Factor VIII (FVIII) is a 2332 amino acid glycoprotein with domain organization of A1-A2-B-A3-C1-C2 which is a crucial component of the blood coagulation cascade. After secretion, FVIII circulates in the bloodstream at a concentration of one nanomolar bound to von Willebrand Factor (vWF) which protects FVIII from clearance. In the event of an injury to the bloodstream, FVIII is proteolytically cleaved, releases from vWF and binds to both activated platelet surfaces and activated Factor IX with nanomolar affinity. These interactions increase the rate of blood clot formation 100,000 fold. Hemophilia A is an x-linked recessive disease affecting 1 in 5000 …