Structure of the Human Factor VIII C2 Domain in Complex with the 3E6 Inhibitory Antibody.

ABSTRACT: Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into "classical" and "non-classical" inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conserved when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously.

SUBMITTER: Wuerth ME 

PROVIDER: S-EPMC4657047 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature