Anti-fVIII C2 domain epitope mapping and modeling of PL membrane binding. (A) Superposition of the C2 domain/3E6/G99 ternary complex with the C2 domain/BO2C11 binary complex; red: ternary complex C2 domain, yellow: BO2C11-bound C2 domain, green: G99 F_AB, blue/cyan: 3E6 F_AB, orange: BO2C11 F_AB. The BO2C11 and 3E6 antibodies inhibit binding of fVIII to PL membranes. (B,C) Model for PL membrane association by the fVIII C2 domain based on epitope mapping; (B) ribbon diagram with basic and surface-exposed hydrophobic residues and proposed PL membrane position highlighted; (C) electrostatic surface potential for the fVIII C2 domain in the same orientation as in B, blue: positive charge, red: negative charge. The surface potentials were calculated and displayed as in Figures 2 and 3.