THROMBOSIS AND HEMOSTASIS A novel calcium-binding site of von Willebrand factor A2 domain regulates its cleavage by ADAMTS13
نویسندگان
چکیده
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 Society Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; 4Huashan Hospital, Fudan Medical School, Shanghai, China; 5Immune Disease Institute, Children’s Hospital Boston and Department of Pathology, Harvard Medical School, Boston, MA; and 6Heidelberg Institute for Theoretical Studies, Heidelberg, Germany
منابع مشابه
THROMBOSIS AND HEMOSTASIS A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF
ADAMTS13 metalloprotease regulates the multimeric size of von Willebrand factor (VWF) by cleaving the Tyr1605-Met1606 bond in the VWF A2 domain. The mechanisms of VWF recognition by ADAMTS13 have yet to be fully resolved. Most studies have focused on the role of exosites within the VWF A2 domain, involved in interaction with the ADAMTS13 spacer domain. In the present study, we expressed differe...
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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 Essential role of the disintegrin-like domain in ADAMTS13 function
ADAMTS13 is a highly specific multidomain plasma metalloprotease that regulates the multimeric size and function of von Willebrand factor (VWF) through cleavage at a single site in the VWF A2 domain. The precise role that the ADAMTS13 disintegrin-like domain plays in its function remains uncertain. Truncated ADAMTS13 variants suggested the importance of the disintegrin-like domain for both enzy...
متن کاملMechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor.
Von Willebrand factor (VWF) is secreted as ultralarge multimers that are cleaved in the A2 domain by the metalloprotease ADAMTS13 to give smaller multimers. Cleaved VWF is activated by hydrodynamic forces found in arteriolar bleeding to promote hemostasis, whereas uncleaved VWF is activated at lower, physiologic shear stresses and causes thrombosis. Single-molecule experiments demonstrate that ...
متن کاملTHROMBOSIS AND HEMOSTASIS Amino acid residues Arg659, Arg660, and Tyr661 in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factor
Previous studies have shown that ADAMTS13 spacer domain is required for cleavage of von Willebrand factor (VWF). However, the exact amino acid residues within this domain critical for substrate recognition are not known. Epitope mapping of anti-ADAMTS13 immunoglobulin G from patients with thrombotic thrombocytopenic purpura and sequence alignment of the ADAMTS13 spacer domains of human, mouse, ...
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