Domain structure of VWF and VWF fragments. Each VWF subunit is composed of multiple domains. The expected valency for the mature form of each VWF fragment is described in the “Methods” section. SS denotes the VWF signal sequence. The D1 and D2 domains (A23-R763) compose the VWF propeptide. Furin cleaves between R763 and S764. The amino acid sequence for a minimal, proteolytic VWF fragment previously found to bind FVIII (S764-R1035)¹⁴  lies in the D′ and D3 domains. The approximate locations of disulfide bonds that result in dimerization or multimerization/concatemerization of VWF subunits are indicated. VWF domains contained within each subcloned VWF fragment are depicted as white boxes (deletion is indicated by dashed line). The position of the E and FLAG tags is indicated by the black box. GS denotes glycine-serine–rich linker. The Fc residues (G242-K463) for D′D3-Fc are numbered according to the coding sequence of the mRNA for Mus musculus immunoglobulin heavy chain complex (GenBank# BC003435).