Model of factor VIII interacting with phospholipid membrane. Front and side view of factor VIII crystal structure (PDB ID: 3CDZ) anchored into a phospholipid membrane (light gray). Green represents A1 domain (residues 1-336); pink, A2 domain (residues 373-721); gold-brown, A3 domain (residues 1690-2019); medium gray, C1 domain (residues 2020-2172), with mutated residues encompassing the lower surface highlighted by coloring; dark gray, C2 domain (residues 2172-2332); and orange spheres, 4 membrane-interactive hydrophobic residues. The epitopes of anti-C2 domain mAb ESH4 (blue and yellow-orange) and BO2C11 (orange and yellow-orange) are highlighted by coloring.