A model of 2-site binding of ADAMTS13 to ULVWF. (A) Alignments of the sequences of the CUB-1 domain of ADAMTS13 and the CUB domains of 2 spermadhesins. (B) Four of the 5 peptides were located in the third and fourth β-strands of the CUB fold, indicating that this region is involved in binding ULVWF. One peptide was derived from the C-terminus that potentially interacts with the third and fourth β-strands. (C) A 2-site model of ADAMTS13 binding to ULVWF. ADAMTS13 exists in plasma in open and closed states that are in equilibrium, with the closed state being the dominant form. The binding of ADAMTS13 through its CUB-1 domain to ULVWF anchored to the surface of endothelial cells is facilitated by fluid shear stress. Once bound, ADAMTS13 assumes the open conformation that exposes the second cryptic binding site to stabilize the interaction with ULVWF.