(A) Schematic domain structure of ADAMTS13. Human ADAMTS13 is composed of a catalytic region (ie, metalloprotease domain [MP]) and noncatalytic region that is divided into 3 parts: the proximal, middle, and distal. The proximal noncatalytic part has a disintegrin domain (Dis), first thrombospondin type 1 (TSP1) repeat, a cysteine-rich domain (Cys), and a spacer domain. The middle and distal noncatalytic regions contain 7 more TSP1 repeats and CUB domain, respectively. (B) Homolog model of the metalloprotease and disintegrin domains of ADAMTS13. The metalloprotease domain is shown in light blue. Three active sites His and catalytic residues Glu (dark blue) coordinates a catalytic Zn²⁺ ion (pink). The disintegrin domain is depicted in light green, light pink, and red. The hypervariable region (HVR) is highlighted in light pink with Arg349 and Leu350 highlighted in red. These 3 amino acids lie adjacent to the active site cleft. Arg349 is located approximately 26 Å from the active site Zn²⁺. See the complete figure in the article beginning on page 5609.