METALLOPROTEASE ADAMTS-13
https://doi.org/10.35754/0234-5730-2019-64-4-471-482
Abstract
Introduction. The signifi cance of ADAMTS-13 extends beyond its key role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP); there is evidence of a relationship between a decrease in the ADAMTS-13 activity and thrombotic events in acute myocardial infarction and ischemic stroke.
Aim. To generalise available information on the structure and function of the metalloprotease ADAMTS-13.
General findings. The biological function of ADAMTS-13 consists in the cleavage of ultra-large von Willebrand factor (vWF) multimers. The fact that its defi ciency causes the development of TTP provides a basis for understanding the function of vWF–cleaving protease. ADAMTS-13 has a domain structure. The functional roles of most ADAMTS-13 domains, as well as the key role of the ADAMTS-13-vWF interaction in the regulation of haemostasis, are defi ned. The conformational activation of ADAMTS-13 by vWF constitutes an important aspect of its function. After getting into the bloodstream, ultra-large vWF multimers quickly adopt a closed conformation, which becomes very resistant to ADAMTS-13 proteolysis in the absence of shear stress. Ultra-large plasma vWF multimers regain their sensitivity to ADAMTS-13 after being exposed to high fl uid shear stress, which unfolds the central vWF-A2 domain. The unfolding of a vWF molecule under shear stress conditions reveals previously hidden exosites in domain A2, which gradually increase the binding affi nity between ADAMTS-13 and vWF. The mechanism underlying the production of autoantibodies against ADAMTS-13 is unknown and requires further study. The masking of cryptic epitopes in the closed conformation of ADAMTS-13 prevents the formation of autoantibodies. Early antigen recognition of ADAMTS-13 occurs through surface-exposed epitopes in the C-terminal domains. More detailed information on the mechanisms underlying the interaction between ADAMTS-13 and the vWF can improve the understanding of mechanisms involved in the regulation of the coagulation system.
Conflict of interest: the authors declare no confl ict of interest.
Financial disclosure: the study had no sponsorship.
About the Authors
A. V. Koloskov
North-Western State Medical University named after I.I. Mechnikov
Russian Federation
Russian Federation
Andrey V. Koloskov, Dr. Sci. (Med.), Prof., Head of the Department for Hematology and Transfusiology
tel.: +7 (812) 948-09-17
A. A. Mangushlo
North-Western State Medical University named after I.I. Mechnikov
Russian Federation
Russian Federation
Alexander A. Mangushlo, Postgraduate Researcher, Department for Hematology and Transfusiology
tel.: +7 (812) 948-09-17
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For citations:
Koloskov A.V., Mangushlo A.A. METALLOPROTEASE ADAMTS-13. Russian journal of hematology and transfusiology. 2019;64(4):471–482. (In Russ.) https://doi.org/10.35754/0234-5730-2019-64-4-471-482
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