Details of the C1-C2 domain orientation and C2–membrane-binding region derived from the FVIII model.

Panel A shows the Cα trace of the C1-C2 domains as fitted within the FVIII 3D map. The main β strands are depicted as flattened ribbons. Intradomain disulfide bonds are shown in yellow and the cysteine Cα atoms as yellow spheres. The glycosylated Asn2118 residue is shown as a brown sphere. The 4 predicted membrane-binding loops of the C2 domain are shown in green with the loop residues numbered. Panel B shows the surface representation of the C1-C2 domains in the same orientation and domain coloring as in panel A. Some hydrophobic residues (see text) predicted in our model to have direct contact with the A1 and A3 domains are shown in white. Panels C and D show the membrane-binding region of the C2 domain viewed along the x-axis (panel C) and rotated clockwise 10° around the z-axis (panel D). The Cα chain (blue ribbon) is fitted within the 3D map (0.4ς blue contour). The hydrophobic side chains and residue numbers of the 4 loops inserting into the membrane are shown in green. The side chains of 3 lysine residues predicted to interact electrostatically with phosphatidyl serine head groups from the phospholipid surface (white dashed line) are shown in red.