(A) Schematic representation of human ADAMTS13 domain structure. The C-terminal TSP1 (T1) 2-8 and CUB domains are proposed to interact with the spacer domain. (B) Two different views of the 3-dimensional structure of the MDTCS fragment. Here, M, the metalloprotease domain, is modeled; the disintegrin domain (D), first thrombospondin type 1 repeat (T), Cys-rich domain (C), and spacer domain (S) are crystallized.¹¹ A part of the unraveled central A2 domain of VWF (thick green dotted line) may interact with MDTCS on 3 identified exosites (dashed circles) including the surface charged residues R660, Y661, and Y665 in the spacer domain, a hydrophobic pocket involving A472, A473, V474, and H476 (H476N/Q478T, Gly3) in the Cys-rich domain, and a nonconserved region involving R349 and L350 in the disintegrin domain. Adapted from Figure 6 in the article by de Groot et al that begins on page 1968.