danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8323-2023-67-1-38-40dan-1109Research ArticleБИОЛОГИЯBIOLOGYСтруктурное обоснование активации киназы ZAP-70 при фосфорилировании тирозинов 315, 319 и 493Structural basis of ZAP-70 activation upon phosphorylation of tyrosines 315, 319 and 493УрбанВ. А.UrbanV. A.

Урбан Виктор Андреевич – мл. науч. сотрудник

ул. Академическая, 27, 220072, Минск

Urban Viktar A. – Junior Researcher

27, Akademicheskaya Str., 220072,Minsk

urban@ibp.org.byВересовВ. Г.VeresovV. G.

Вересов Валерий Гавриилович – д-р биол. наук, гл. науч. сотрудник

ул. Академическая, 27, 220072, Минск

Veresov Valery G. – D. Sc. (Biology), Chief Researcher

27, Akademicheskaya Str., 220072,Minsk

veresov@ibp.org.byИнститут биофизики и клеточной инженерии Национальной академии наук БеларусиInstitute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus2023040320236713840Copyright © Урбан В.А., Вересов В.Г., 20232023Урбан В.А., Вересов В.Г.Urban V.A., Veresov V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://doklady.belnauka.by/jour/article/view/1109

Тирозиновая киназа ZAP-70 (Zeta-chain-Associated Protein kinase 70) является ключевым ферментом в регуляции адаптивного иммунного ответа. Cвязываясь своими SH2-доменами с цитоплазматическим доменом белка CD3ζ, ассоциированного с T-клеточным рецептором, Zap-70 осуществляет передачу активационного сигнала к T-лимфоцитам, индуцированного взаимодействием главного комплекса гистосовместимости с T-клеточным рецептором. Известно, что для киназной активации ZAP-70 также необходимым является фосфорилирование тирозинов 315, 319 и 493, однако механизмы активации неясны. В настоящем исследовании использованы средства молекулярной структурной биологии для установления этих механизмов.

ZAP-70 (Zeta-chain-Associated Protein kinase 70) is a key kinase in the regulation of the adaptive immune response. Zap-70 acts by binding its SH2-domains to the T-cell-associated CD3ζ protein, thus transmitting a T-cell activation signal induced by the interaction of Major Histocompatibility Complex with T-cell Receptor. It has been established that for ZAP-70 kinase activation, the phosphorylation of Tyr315, Tyr319, and Tyr493 is required, however the mechanisms are unclear. In the present study, we use the tools of structural modeling to elucidate the ZAP-70 activation mechanisms.

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