VWF structure and binding sites in relationship to the VWFpp mutation.

(A) The protein schematic of the pre-pro-VWF molecule. The propeptide (VWFpp) is 741 aa's with a 22-aa signal peptide, and is cleaved intracellularly at residue 763. Mature VWF is 2050 aa's in length. (B) Structure and function of VWF domains. The modular array of the repeating domains of VWFpp and VWF is shown. Several known functions of VWF have been mapped specifically to domains, listed below the drawing. The s-s sites shown for the D1 and D2 domains represent the vicinal cystines. The —S— depicts the intermolecular cystines, which bridge the VWF monomers into dimers (C2) and multimers (D3). The functional A1 and A3 loops are also depicted, above the domains. (C) The cDNA structure of the VWF. The different VWD mutations, types IIC, 2N, 2B, 2M, and 2A, are listed below along with the site of the Tyr87Ser defect.