Stereo diagram of superimposed structures of the recombinant factor VIII C2 domain in the free and antibody-bound crystal forms.

(A) The free and Fab-complexed C2 proteins are shown in blue and green, respectively. The structure of the β core is virtually identical in the 2 structures. Most of the deviations between the structures occur at or near the 2 hydrophobic β-hairpin turns at the bottom of the figure. The plane formed by the 2 strands of the second β hairpin (residues 2197 to 2203) moves to a position perpendicular to that seen in the unbound C2-domain structure. The ψ angle of M2199 rotates from −11° to +122°, whereas in F2200, the φ and ψ angles rotate from −99° to +56° and from −23° to +26°, respectively. This region interacts with residues in CDR-H1, CDR-H2, and CDR-H3 of the heavy chain as well as with sites on CDR-L1 and CDR-L3 of the light chain. (B) Rotations about backbone dihedral angles in the β hairpin containing residues N2198 through A2201 shift the orientation of these side chains by up to 5 Å.