bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2019-64-4-471-482bloodjour-167Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWS OF LITERATUREМЕТАЛЛОПРОТЕАЗА ADAMTS-13METALLOPROTEASE ADAMTS-13https://orcid.org/0000-0002-5249-4255КолосковА. В.KoloskovA. V.

Колосков Андрей Викторович, доктор медицинских наук, профессор, заведующий кафедрой гематологии и трансфузиологии 

тел.: +7 (812) 948-09-17

Andrey V. Koloskov, Dr. Sci. (Med.), Prof., Head of the Department for Hematology and Transfusiology 

tel.: +7 (812) 948-09-17

Andrei.Koloskov@szgmu.ruhttps://orcid.org/0000-0002-3163-5194МангушлоА. А.MangushloA. A.

Мангушло Александр Александрович, аспирант кафедры гематологии и трансфузиологии 

тел.: +7 (812) 948-09-17

Alexander A. Mangushlo, Postgraduate Researcher, Department for Hematology and Transfusiology

tel.: +7 (812) 948-09-17

sutura@mail.ruФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Министерства здравоохранения Российской ФедерацииРоссияNorth-Western State Medical University named after I.I. MechnikovRussian Federation201912122019644471–482Copyright © Колосков А.В., Мангушло А.А., 20192019Колосков А.В., Мангушло А.А.Koloskov A.V., Mangushlo A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/167Ведение

Ведение. Значение открытия металлопротеазы ADAMTS-13 выходит за рамки представления о ее ключевой роли в патогенезе тромботической тромбоцитопенической пурпуры (ТТП), имеются данные о наличии связи между снижением активности ADAMTS-13 и тромботическими событиями при остром инфаркте миокарда и ишемическом инсульте.

Цель обзора — обобщение современной информации о структуре и функции металлопротеазы ADAMTS-13.

Основные сведения

Основные сведения. Биологической функцией протеазы ADAMTS-13  является расщепление сверхкрупных мультимеров фактора Виллебранда. Основой для понимания функции расщепляющей фактор Виллебранда протеазы явилась демонстрация того, что дефицит ее является причиной развития ТТП. ADAMTS-13 имеет доменную структуру. Установлено функциональное значение большинства доменов ADAMTS-13, ключевая роль взаимодействия ADAMTS-13 и WF в регуляции гемостаза. Конформационная активация протеазы ADAMTS-13  фактором Виллебранда является важным аспектом реализации ее функции. После попадания в кровоток сверхкрупные мультимеры фактора Виллебранда быстро принимают закрытую конформацию, которая становится очень устойчивой к протеолизу ADAMTS-13 при отсутствии напряжения сдвига. Плазменные сверхкрупные мультимеры фактора Виллебранда восстанавливает свою чувствительность к ADAMTS-13 при воздействии высокого напряжения сдвига жидкости, которое разворачивает центральный домен А2 фактора Виллебранда. Развертывание молекулы фактора Виллебранда под воздействием напряжения сдвига открывают в домене А2  ранее скрытые экзосайты, которые постепенно увеличивают сродство связывания между ADAMTS-13  и фактором Виллебранда. Механизм выработки аутоантител против ADAMTS-13 неизвестен и требует дальнейшего изучения. Маскировка криптических эпитопов в  замкнутой конформации ADAMTS-13  предотвращает образование аутоантител. Раннее антигенное распознавание ADAMTS-13 происходит через поверхностные обнаженные эпитопы в С-концевых доменах. Более подробная информация о механизмах взаимодействия между ADAMTS-13 и фактором Виллебранда может улучшить понимание механизмов регуляции свертывающей системы.

Конфликт интересов

Конфликт интересов: авторы заявляют об отсутствии конфликта интересов.

Финансирование

Финансирование: исследование не имело спонсорской поддержки.

Introduction

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

Aim. To generalise available information on the structure and function of the metalloprotease ADAMTS-13.

General findings

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

Conflict of interest: the authors declare no confl ict of interest.

Financial disclosure

Financial disclosure: the study had no sponsorship.

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The authors declare that there are no conflicts of interest present.