UniProt domain structure of mature VWF and the C-domain fragments analyzed in this study. The mature N-terminus begins with a protease inhibitor I8 domain (I8, residues 772-828), followed by a D domain (residues 856-1074), a cysteine-rich domain (CR, residues 1053-1127), another I8 domain (residues 1140-1196), 3 type A domains (residues 1275-1458, 1496-1669 and 1689-1871), another D (residues 1938-2153) and I8 (residues 2199-2255) domain, 3 type C domains (residues 2255-2328, 2429-2495 and 2580-2645), and finishes with the C-terminal knot (CK, residues 2724-2812). Fragments encompassing the C1-CK (residues 2255-2813), C1-C3 (residues 2255-2648), and C2 (residues 2429-2495) domains were expressed in mammalian HEK cells and purified from the conditioned medium. The residue numbering is that for the preproprotein.