Electron density at residues involved in critical interactions of the binding interface.

The first antigenic peptide of C2 (residues 2250 to 2253), corresponding to an exposed hydrophobic β turn containing L2251 and 2252, forms primarily hydrophobic interactions with residues from CDR-H1, CDR-H3, and the amino terminus of the heavy chain (A). The second antigenic region from C2 (residues 2197 to 2203), corresponding to a second exposed hydrophobic β turn containing M2199 and F2200, exhibits more extensive van der Waals contact with the Fab surface, and there are more polar interactions than in the first epitope (B). Two R residues from the C2 domain, both of which are proposed to interact with anionic lipid head groups when factor VIII binds to platelet membranes, form salt links with D residues on the Fab surface. R2220 lies within a cleft between the 2 hydrophobic hairpin turns (C) and interacts with D102 of the heavy chain. R2215 resides on the third loop at this end of the C2 molecule and interacts with D52 of the heavy chain (D). An adjacent loop contains residues Q2222 and V2223, which contact the Fab surface directly (E). V2223 is another hydrophobic residue that was solvent-exposed in the free C2 structure, and it was proposed that it may make additional contacts with membrane surfaces. Finally, residues H2315 and Q2316 participate in polar interactions with specific residues and buried water molecules at the C2-Fab interface (F). See Table 2 for a list of all contacts in this interface.