Human Factor VIII Structure & Function
Technician Amy Griffiths working in the Fay Lab
Factor VIII serves as a protein cofactor for the serine protease, factor IXa in the membrane-dependent conversion of factor X to factor Xa during the blood coagulation cascade reactions. Deficiency or defects in factor VIII result in hemophilia A, the most common of the severe, inherited bleeding disorders. Ongoing studies in our laboratory include physical and biochemical analyses of factor VIII structure, inter-subunit interactions, and intermolecular interactions with other components of the clotting cascade. Overall, our research program is aimed at gaining fundamental insights into the structure, activity and regulation of a protein central to hemostasis. This information will have specific implications for understanding hemophilia A and developing superior therapeutics for its treatment.
- Residues flanking scissile bonds in Factor VIII modulate rates of cleavage and proteolytic activation catalyzed by Factor Xa. Biochemistry. 52, 8060-8. (2013 Nov 12).
- Replacing the factor VIII C1 domain with a second C2 domain reduces factor VIII stability and affinity for factor IXa. J Biol Chem. 288, 31289-97. (2013 Oct 25).
- Modification of interdomain interfaces within the A3C1C2 subunit of factor VIII affects its stability and activity. Biochemistry. 52, 3921-9. (2013 Jun 04).