Characterization of a core binding site for ADAMTS-13 in the A2 domain of von Willebrand factor
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چکیده
منابع مشابه
Characterization of a core binding site for ADAMTS-13 in the A2 domain of von Willebrand factor.
ADAMTS-13, a metalloprotease in plasma, specifically cleaves the Tyr-1605-Met-1606 bond in the A2 domain of von Willebrand factor (VWF) to regulate the polymer distribution of VWF in circulation, which is critical for primary hemostasis. A 73-aa peptide (VWF73) was previously identified as the minimal substrate cleavable by ADAMTS-13. In this study, VWF73 was enzymatically and chemically cleave...
متن کاملADAMTS‐13 and von Willebrand factor: a dynamic duo
von Willebrand factor (VWF) is a key player in hemostasis, acting as a carrier for factor VIII and capturing platelets at sites of vascular damage. To capture platelets, it must undergo conformational changes, both within its A1 domain and at the macromolecular level through A2 domain unfolding. Its size and this function are regulated by the metalloproteinase ADAMTS-13. Recently, it has been s...
متن کاملA novel calcium-binding site of von Willebrand factor A2 domain regulates its cleavage by ADAMTS13.
The proteolysis of VWF by ADAMTS13 is an essential step in the regulation of its hemostatic and thrombogenic potential. The cleavage occurs at strand β4 in the structural core of the A2 domain of VWF, so unfolding of the A2 domain is a prerequisite for cleavage. In the present study, we present the crystal structure of an engineered A2 domain that exhibits a significant difference in the α3-β4 ...
متن کاملForce Sensitivity of the Von Willebrand Factor A2 Domain
von Willebrand factor (VWF) is a multimeric glycoprotein that critically supports platelet aggregation in hemostasis. Disordered VWF function causes both thrombotic and bleeding disorders, and genetic defects in VWF are responsible for von Willebrand’s disease (VWD), the most common inherited bleeding disorder in humans. Very large VWF multimers exhibit the greatest thrombogenic activity, which...
متن کاملTHROMBOSIS AND HEMOSTASIS A novel calcium-binding site of von Willebrand factor A2 domain regulates its cleavage by ADAMTS13
1State Key Laboratory of Molecular Biology and Research Center for Structural Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and 2Graduate School of Chinese Academy of Sciences, Shanghai, China; 3Key Laboratory of Computational Biology of Chinese Academy of Sciences, Chinese Academy of Sciences and German Max Planck...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2006
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.0609190103