Fig. 1.

Activation of ADAMTS13 by autoantibodies from a patient with TTP or by low pH. (A) Structure of ADAMTS13. (B) Fluorogenic substrates terminate at VWF residues indicated by arrows. Each substrate has Lys¹⁶¹⁷ replaced with Arg, N-terminal Gly modified with IRDye QC-1 (QC1), and Asn¹⁶¹⁰ replaced by Cys and modified with DyLight 633 (DyL) (22). The arrowhead indicates the cleaved Tyr-Met bond. Secondary structure elements of the VWF A2 domain (11) are indicated below and segments that interact with specific ADAMTS13 domains (13) are indicated above the sequence. (C) BCW49 plasma activated ADAMTS13 with a titer of 9.6 U at pH 7.4 (orange squares), but not at pH 6.0 (orange circle). BCW49 plasma did not activate MDTCS at pH 6 (blue circle) or pH 7.4 (blue circle). (D) Rates of VWF71 cleavage were determined as a function of pH for ADAMTS13 (orange circles) and MDTCS (blue circles). Error bars indicate 95% confidence intervals and if not shown are smaller than the symbols.