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Physical Sciences and Mathematics Commons

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Chemistry

WWU Graduate School Collection

Theses/Dissertations

2021

Hemophilia A

Articles 1 - 2 of 2

Full-Text Articles in Physical Sciences and Mathematics

Structural Studies Of The Von Willebrand Factor D’ Domain And Its Binding Mechanism To Factor Viii, Ap Wang Jan 2021

Structural Studies Of The Von Willebrand Factor D’ Domain And Its Binding Mechanism To Factor Viii, Ap Wang

WWU Graduate School Collection

Hemophilia A is an X-linked disorder that results in uncontrolled bleeding, which is caused by a lack of activity for blood coagulation factor VIII, an essential protein cofactor in the clotting cascade. Factor VIII consists of multiple domains, and binding disruptions between factor VIII and its circulatory partner, von Willebrand Factor, may cause von Willebrand disease. Von Willebrand Disease type 2N is an autosomal recessive disease, and it is caused by binding disruptions between the D’ domain (also known as TIL’E’) of von Willebrand Factor and a3 domain of factor VIII. A 2.9Å Cryoelectron microscopy structure of the FVIII:vWF complex …


Structural And Mutational Characterization Of The Blood Coagulation Factor Viii C Domain Lipid Binding Interface, Shaun C. Peters Jan 2021

Structural And Mutational Characterization Of The Blood Coagulation Factor Viii C Domain Lipid Binding Interface, Shaun C. Peters

WWU Graduate School Collection

Blood coagulation factor VIII (fVIII) functions as a cofactor in the blood coagulation cascade for proteolytic activation of factor X by factor IXa. During coagulation, fVIII is activated and subsequently binds to activated platelet surfaces by coordination of the fVIII C1 and C2 domains to the exposed phosphatidylserine of activated platelet membranes. Structural and mutational studies have suggested that both hydrophobic and electrostatic interactions occur between the two tandem C domains and activated lipid surfaces, but models of C domain phospholipid binding propose conflicting regions that directly interact with the membrane surface. This thesis reports the determination of the molecular …