tailieunhanh - Báo cáo khoa học: Interaction of the cysteine-rich domain of snake venom metalloproteinases with the A1 domain of von Willebrand factor promotes site-specific proteolysis of von Willebrand factor and inhibition of von Willebrand factor-mediated platelet aggregation

Snake venom metalloproteinases (SVMPs) have recently been shown to interact with proteins containing von Willebrand factor A (VWA) domains, including the extracellular matrix proteins collagen XII, collagen XIV, mat-rilins 1, 3 and 4, and von Willebrand factor (VWF) via their cysteine-rich domain. | ỊFEBS Journal Interaction of the cysteine-rich domain of snake venom metalloproteinases with the A1 domain of von Willebrand factor promotes site-specific proteolysis of von Willebrand factor and inhibition of von Willebrand factor-mediated platelet aggregation Solange M. T. Serrano1 Deyu Wang2 John D. Shannon2 Antonio F. M. Pinto3 Renata K. Polanowska-Grabowska4 and Jay W. Fox2 1 Laboratorio Especialde Toxinologia Aplicada and CAT-CEPID Instituto Butantan Sao Paulo Brazil 2 Department of Microbiology University of Virginia Charlottesville VA USA 3 Centro de Biotecnologia Universidade Federaldo Rio Grande do Sul Porto Alegre Brazil 4 Department of Biochemistry and Molecular Genetics University of Virginia Charlottesville VA USA Keywords cysteine-rich domain platelet aggregation snake venom metalloproteinase von Willebrand factor VWA Correspondence J. W. Fox Department of Microbiology University of Virginia PO Box 800734 Charlottesville VA 22908-0734 USA Tel 1 434 924 0050 E-mail jwf8x@ Received 2 March 2007 revised April 15 2007 accepted 18 May 2007 doi Snake venom metalloproteinases SVMPs have recently been shown to interact with proteins containing von Willebrand factor A VWA domains including the extracellular matrix proteins collagen XII collagen XIV mat-rilins 1 3 and 4 and von Willebrand factor VWF via their cysteine-rich domain. We extended those studies using surface plasmon resonance to investigate the interaction of SVMPs with VWF and demonstrated that jararhagin a PIII SVMP containing a metalloproteinase domain followed by disintegrin-like and cysteine-rich domains catrocollastatin C a disinte-grin-like cysteine-rich protein and the recombinant cysteine-rich domain of atrolysin A A C all interacted with immobilized VWF in a dosedependent fashion. Binding of VWF in solution to immobilized A C was inhibited by ristocetin and preincubation of platelets with A C abolished ristocetin VWF-induced platelet .