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Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-03-0908. This Article Full Text (PDF) All Versions of this Article: 2003-03-0908v1 102/9/3232    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Soejima, K. Articles by Nakagaki, T. Search for Related Content PubMed PubMed Citation Articles by Soejima, K. Articles by Nakagaki, T. Social Bookmarking                   What's this? Submitted March 27, 2003 Accepted July 8, 2003 ADAMTS-13 cysteine-rich/spacer domains are functionally essential for von Willebrand factor cleavage Kenji Soejima*, Masanori Matsumoto, Koichi Kokame, Hideo Yagi, Hiromichi Ishizashi, Hiroaki Maeda, Chikateru Nozaki, Toshiyuki Miyata, Yoshihiro Fujimura, and Tomohiro Nakagaki First Research Department, The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan National Cardiovascular Center Research Institute, Osaka, Japan Department of Health Science, Nara Medical University, Nara, Japan * Corresponding author; email: soejima{at}kaketsuken.or.jp. A severe lack of von Willebrand factor-cleaving protease (VWF-CP) activity can cause thrombotic thrombocytopenic purpura (TTP). This protease was recently identified as a member of the ADAMTS family, ADAMTS-13. It consists of a preproregion, a metalloprotease domain, a disintegrin-like domain, a thrombospondin type-1 motif (Tsp1), a cysteine-rich domain, a spacer domain, additional Tsp1 repeats, and CUB domains. To explore the structure and function relationships of ADAMTS-13, we prepared here 13 sequential COOH-terminal truncated mutants and a single-point mutant (RGD to RGE in the cysteine-rich domain), and compared the activity of each mutant with that of the wild-type protein. The results revealed that the truncation of the cysteine-rich/spacer domains caused a remarkable reduction in VWF-CP activity. We also prepared IgG fractions containing inhibitory autoantibodies against ADAMTS-13 from plasma from three patients with acquired TTP, and performed mapping of their epitopes using the aforementioned mutants. The major epitopes of these antibodies were found to reside within the cysteine-rich/spacer domains. 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