Schematic representation of the old and new domain arrangement of VWF. The molecular architecture of VWF is characterized by the presence of distinct domain structures. (A) The arrangement of 5 different domain structures according to the original analysis of the VWF sequence (reviewed by Pannekoek and Voorberg).4 The numbering of the domain boundaries has been used in our laboratory in previous years. (B) The domain organization as has been recently proposed by Zhou et al.5 One striking difference with the original domain structure is the replacement of the B1-3-C1-C2 domain region by 6 homologous C domains. In addition, their analysis revealed that the D domains consist of various independent structures, which are highlighted in panel (C). The D1, D2, and D3 domains each contain a VW domain, a trypsin inhibitor-like structure, a C8 fold, and an E module. The D′ region lacks the VW domain and C8 fold. The D4 domain lacks the E module, but instead comprises a unique sequence designated D4N. Adapted from Rauch et al6 with permission.
