Conformational change in VWF C8-3 and TIL3 during dimerization. (A-B) Comparison of monomeric crystal structure model (A) and dimeric homology model (B) of D3. The monomer on the left is color-coded identically in panels A and B. Each module is labeled and has a distinct color for carbon atoms, except regions that change substantially in conformation upon dimerization are colored magenta. The other monomer on the right in the dimer in panel B lacks the color code for conformational change and its modules are shown in slightly different colors than in panel A. Its module and side-chain names are distinguished with an appended apostrophe. Side chains of cysteines and other selected residues are shown as sticks with yellow sulfurs and red oxygens. Additionally, sulfur atoms of cysteines in the triad in C8-3 and C1142 in TIL3 are shown as spheres. Dashed black arrows represent vectors for change in position of the sulfur atoms. Backbone Cα atoms of Cys triad residues are connected with cyan lines in panel A. The hydrogen bonds between the Asp-1096 side chain and main chain of the other monomer in the dimer are shown as red dashed lines for 1 of 2 reciprocal interactions in panel B. (C) Sequence alignment of the cysteine triad in human VWF and gel-like mucins. In VWF and MUC2, cysteines in intrachain disulfides are green and those as free cysteines in the VWF monomer or in interchain linkages in dimers are red. Cysteines in other mucins are black; however, 4 have cysteine triad sequences highly identical among VWF and 4 mucins and are predicted to undergo disulfide exchange between monomers and dimers, like VWF. MUC19 differs substantially in the same region, including having only 1 cysteine. It is predicted to be free in the monomer and disulfide linked in the dimer, much like Cys-1142 in VWF and its equivalent in all gel-like mucins.