Membrane-bound FVIII model.

The FVIII model is shown anchored into the top of a phospholipid membrane (colored white). The β strands are shown as flattened ribbons. A1 domain (residues 1-336) is in red with magenta β strands. A2 domain (residues 376-716) is in yellow with silver β strands and A3 domain (residues 1692-2020) is in green with β strands also in green. C1 and C2 domains and β strands are in gold-brown and blue, respectively. Short α helices within the A domains are presented as light-blue spirals. The 4 predicted membrane-binding loops of the C2 domain are shown in green. Domain boundaries were defined thus: A1, from amino acid residues 1 (red sphere) to 336 (white sphere); A2, 376 (yellow sphere) to 716; A3, 1692 to 2020 (green spheres); C1, 2021 to 2170; and C2 2171 to 2332 (blue spheres). Asparagine residues known to be glycosylated (Asn41, Asn239, Asn582, Asn1810, and Asn 2118), are represented with large spheres colored as for the Cα traces of each domain. APC cleavage sites Arg336 and Arg562 are marked by white spheres. The beginning of the A2-B connecting acidic peptide (a2) is shown as residues 712-716 (dashed magenta trace). In C2, peptide 2303 (magenta sphere) to 2332 is also shown in magenta, which is reported to accommodate VWF and membrane binding sites. The side chains of residues, Arg2307 (blue sphere) Ile2098, Ser2119, and Arg2150 (golden-brown sphere) are solvent exposed and implicated in VWf binding.