Analysis of the VWF C domains and joiner regions and predicted structure of the C2 domain of VWF. (A) Alignment of human VWF C domains and joining regions with C domains from hemocytin (silk worm) and hemolectin (fruit fly) using the Clustal 2.1 multiple sequence alignment tool. Insect C domains are derived and numbered as described previously.⁴¹  The 10 disulfide-forming cysteines in C domains are labeled above the alignment. (B) Ribbon structure of the C domain of crossveinless 2 (PDB ID 3BK3) showing the 5 disulfide bonds in yellow. The cysteine residues that form the Cys1-Cys4 and Cys3-Cys5 disulfide bonds are indicated. The X-ray structure has a resolution of 2.7 Å.²⁵  (C) Predicted structure of the C2 domain of VWF. The structure was derived using the crossveinless 2 and procollagen 2A C-domain structures and the I-TASSER protein structure prediction tool.¹⁹  The C-score is −1.05. The cysteine residues are indicated in yellow. Cys2451 and Cys2468 form a disulfide bond in this structure, whereas Cys2431 and Cys2453 are unpaired.