Light Chain of Factor VIII Is Sufficient for Accelerating Cleavage of von Willebrand Factor by ADAMTS13 Metalloprotease
نویسندگان
چکیده
منابع مشابه
von Willebrand factor is a cofactor for thrombin-catalyzed cleavage of the factor VIII light chain.
The proteolytic activation of highly purified, heterodimeric porcine factor VIII and factor VIII-von Willebrand factor complex by thrombin was compared at I 0.17, pH 7.0, 22 degrees C. During the activation of factor VIII, heavy-chain cleavage is necessary to activate the procoagulant function, whereas light-chain cleavage is required to dissociate factor VIII from von Willebrand factor. The ki...
متن کاملExosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloprotease.
Von Willebrand factor (VWF) is a multimeric protein that mediates platelet adhesion at sites of vascular injury, and ADAMTS13 (a disintegrin and metalloprotease with thrombospondin)is a multidomain metalloprotease that limits platelet adhesion by a feedback mechanism in which fluid shear stress induces proteolysis of VWF and prevents disseminated microvascular thrombosis. Cleavage of the Tyr(16...
متن کاملCompromised shear-dependent cleavage of type 2N von Willebrand factor variants by ADAMTS13 in the presence of factor VIII.
Christopher G. Skipwith1,2; Sandra L. Haberichter3; Ashley Gehrand3; X. Long Zheng1,2 1Department of Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia, Pennsylvania, USA; 2The University of Pennsylvania, Philadelphia Perelman School of Medicine, Philadelphia, Pennsylvania, USA; 3Blood Research Institute, Blood Center of Wisconsin, and Department of Pediatrics, Medical C...
متن کاملFactor VIII and platelets synergistically accelerate cleavage of von Willebrand factor by ADAMTS13 under fluid shear stress.
Previous studies have demonstrated that factor VIII (FVIII) or platelets alone increase cleavage of von Willebrand factor (VWF) by ADAMTS13 under mechanically induced shear stresses. We show in this study that the combination of FVIII and platelets at the physiological concentrations is more effective than either one alone. In the absence of FVIII, lyophilized platelets increase the formation o...
متن کاملA model for the conformational activation of the structurally quiescent metalloprotease ADAMTS13 by von willebrand factor
Blood loss is prevented by the multidomain glycoprotein von Willebrand factor (VWF), which binds exposed collagen at damaged vessels and captures platelets. VWF is regulated by the metalloprotease ADAMTS13, which in turn is conformationally activated by VWF. To delineate the structural requirements for VWF-mediated conformational activation of ADAMTS13, we performed binding and functional studi...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2012
ISSN: 0021-9258
DOI: 10.1074/jbc.m112.390690