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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4139-4145. Prepublished online as a Blood First Edition Paper on September 1, 2005; DOI 10.1182/blood-2005-05-2029. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-2029v1 106/13/4139    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Tao, Z. Articles by Dong, J.-f. Search for Related Content PubMed PubMed Citation Articles by Tao, Z. Articles by Dong, J.-f. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Recombinant CUB-1 domain polypeptide inhibits the cleavage of ULVWF strings by ADAMTS13 under flow conditions Zhenyin Tao, Yuandong Peng, Leticia Nolasco, Santiago Cal, Carlos Lopez-Otin, Renhao Li, Joel L. Moake, José A. López, and Jing-fei Dong From the Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, and the Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, TX; and the Department of Biochemistry and Molecular Biology, University of Oviedo, Spain. The metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motif) converts the hyperreactive unusually large (UL) forms of von Willebrand factor (VWF) that are newly released from endothelial cells into less active plasma forms by cleaving a peptide bond in the VWF A2 domain. Familial or acquired deficiency of this metalloprotease is associated with thrombotic thrombocytopenic purpura (TTP). ADAMTS13 belongs to the ADAMTS metalloprotease family, but, unlike other members, it also contains 2 C-terminal CUB domains (complement component Clr/Cls, Uegf, and bone morphogenic protein 1). Mutations in the CUB region have been found in congenital TTP, but deletion of the region did not impair enzyme activity in conventional in vitro assays. We investigated the functions of the CUB domain in ADAMTS13 activity under flow conditions. We found that recombinant CUB-1 and CUB-1+2 polypeptides and synthetic peptides derived from CUB-1 partially blocked the cleavage of ULVWF by ADAMTS13 on the surface of endothelial cells under flow. The polypeptide bound immobilized and soluble forms of ULVWF, and blocked the adhesion of ADAMTS13-coated beads to immobilized ULVWF under flow. These results suggest that the CUB-1 domain may serve as the docking site for ADAMTS13 to bind ULVWF under flow, a critical step to initiate ULVWF proteolysis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Zhang, W. Pan, A. H. Rux, B. S. Sachais, and X. L. Zheng The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow Blood, September 15, 2007; 110(6): 1887 - 1894. [Abstract] [Full Text] [PDF] K. C. Desch and D. G. Motto Thrombotic Thrombocytopenic Purpura in Humans and Mice Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1901 - 1908. [Abstract] [Full Text] [PDF] W. Zhou, E. E. Bouhassira, and H.-M. Tsai An IAP retrotransposon in the mouse ADAMTS13 gene creates ADAMTS13 variant proteins that are less effective in cleaving von Willebrand factor multimers Blood, August 1, 2007; 110(3): 886 - 893. [Abstract] [Full Text] [PDF] G. Blanc, B. Font, D. Eichenberger, C. Moreau, S. Ricard-Blum, D. J. S. Hulmes, and C. Moali Insights into How CUB Domains Can Exert Specific Functions while Sharing a Common Fold: CONSERVED AND SPECIFIC FEATURES OF THE CUB1 DOMAIN CONTRIBUTE TO THE MOLECULAR BASIS OF PROCOLLAGEN C-PROTEINASE ENHANCER-1 ACTIVITY J. Biol. Chem., June 8, 2007; 282(23): 16924 - 16933. [Abstract] [Full Text] [PDF] N. P Riksen, B. M Luken, I. S Klasen, J. Voorberg, N. Crama, and M. van Deuren Antibodies against the CUB1-2 domains of ADAMTS13 in a patient with benign monoclonal gammopathy: no causal relationship Haematologica, June 1, 2007; 92(6): e74 - e76. [Abstract] [Full Text] [PDF] W. Gao, P. J. Anderson, E. M. Majerus, E. A. Tuley, and J. E. Sadler Exosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloprotease PNAS, December 12, 2006; 103(50): 19099 - 19104. [Abstract] [Full Text] [PDF] C.-j. Liu, W. Kong, K. Xu, Y. Luan, K. Ilalov, B. Sehgal, S. Yu, R. D. Howell, and P. E. Di Cesare ADAMTS-12 Associates with and Degrades Cartilage Oligomeric Matrix Protein J. Biol. Chem., June 9, 2006; 281(23): 15800 - 15808. [Abstract] [Full Text] [PDF] K. Soejima, H. Nakamura, M. Hirashima, W. Morikawa, C. Nozaki, and T. Nakagaki Analysis on the Molecular Species and Concentration of Circulating ADAMTS13 in Blood J. Biochem., January 1, 2006; 139(1): 147 - 154. 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