Structure of the A3 domain/collagen complex. (A) Three-dimensional representation of the VWF A3 domain in complex with a collagen III triple-helical peptide derived from PDB-deposit 4DMU.⁶⁹ Figure was generated using PyMOL software. (B) Three-dimensional representation of nanobody KB-VWF-D3.1 docked onto the A3 domain.⁷⁰ The nanobody’s binding site overlaps the interactive surface involved in collagen binding. Figure was generated using PyMOL software. (C) Two-dimensional representation of the A3 domain. Circles indicate positions of residues where mutations have been associated with reduced collagen binding in patients with von Willebrand disease-type 2M. Note, in the 3-dimensional space, the N- and C-terminal ends of the A3 domain are in close vicinity via a disulfide bridge between Cys¹⁶⁸⁶ and Cys¹⁸⁷².