Biosynthesis and secretion of VWF. (A) Module functions in biosynthesis. (B) Appearance of VWF domains in negative stain EM with class averaging.1,2 Two examples of D1D2 and (D′D3A1)2 class averages are shown. A1-CTCK dimeric bouquet class averages, with averaging centered on different domains, are shown in composite, with (D′D3A1)2 added in the position of A1 separated by dashed lines. Domains that would originate from the same VWF dimer precursor are labeled in white, and those that would originate from other dimers and be disulfide linked during concatemer formation in tubules are labeled in yellow. (C-F) Schematic organization of domains during biosynthesis and secretion based on structural data.1,2,6,19 Dimensions are from Zhou et al1 and Huang et al.6
