Physical Sciences and Mathematics Commons^™

Characterization And Solution Structure Of The Factor Viii C2 Domain In A Ternary Complex With Classical And Non-Classical Inhibitor Antibodies, P. Clint Spiegel, Justin D. Walter, Rachel Werther, Maria S. Polozova, Julie Pohlman, John F. Healey, Shannon L. Meeks, Pete Lollar

Chemistry Faculty and Staff Publications

The most significant complication for patients with severe cases of congenital or acquired hemophilia A is the development of inhibitor antibodies against coagulation factor VIII (fVIII). The C2 domain of fVIII is a significant antigenic target of anti-fVIII antibodies. Here, we have utilized small angle x-ray scattering (SAXS) and biochemical techniques to characterize interactions between two different classes of anti-C2 domain inhibitor antibodies and the isolated C2 domain. Multiple assays indicated that antibodies 3E6 and G99 bind independently to the fVIII C2 domain and can form a stable ternary complex. SAXS-derived numerical estimates of dimensional parameters for all studied complexes …