Model depicting the proposed role of the ADAMTS13 disintegrin-like domain. Homology model of the ADAMTS13 MP-Dis. The metalloprotease domain is shown in light blue showing the 3 active site His and catalytic residues Glu (dark blue) that coordinate a catalytic Zn²⁺ ion (pink). The disintegrin-like 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 amino acids lie adjacent to the active-site cleft. Arg349 is located approximately 26 Å from the active site Zn²⁺. The catalytic efficiency of ADAMTS13 is reduced 10- to 20-fold when either of these residues is mutated. We propose a model in which Asp1614 in the VWF A2 domain (located ∼ 26 Å from the Tyr1605-Met1606 scissile bond) interacts with Arg349 in ADAMTS13. This in turn helps position the scissile bond into the active-site cleft.