Crystal structure and substrate-induced activation of ADAMTS13

Abstract

The plasma metalloprotease ADAMTS13 regulates the platelet-tethering function of von Willebrand factor (VWF) in a shear-dependent manner. Here the authors present the ADAMTS13 crystal structure of the 70kDa N-terminal metalloprotease to spacer domains, and using kinetic measurements they identify a substrate binding induced allosteric mechanism for ADAMTS13, where VWF functions both as an activating cofactor and substrate.