Membrane and Cell BiologyMembrane and Cell BiologyБиологические мембраны0233-47553034-5219The Russian Academy of Sciences36224110.7868/S3034521925060072ArticlesСТАТЬИResearch ArticleX-Domain of nsp-3 Protein of the SARS-CoV-2 Coronavirus Is Capable of Deforming Membranes and Initiating of the Double-Membrane Vesicle Formation Depending on the Cholesterol ContentX-ДОМЕН БЕЛКА NSP-3 КОРОНАВИРУСА SARS-CoV-2 СПОСОБЕН ДЕФОРМИРОВАТЬ МЕМБРАНЫ И ИНИЦИИРОВАТЬ ФОРМИРОВАНИЕ ДВУМЕМБРАННЫХ ВЕЗИКУЛ В ЗАВИСИМОСТИ ОТ СОДЕРЖАНИЯ ХОЛЕСТЕРИНА В СОСТАВЕ МЕМБРАНЫMakhonkoA. AМахонькоА. А-DenievaZ. GДениеваЗ. Г-BatishchevO. VБатищевО. Вolegbati@gmail.comFrumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of SciencesИнститут физической химии и электрохимии им. А.Н. Фрумкина РАН15122025426VOL 42, NO6 (2025)ТОМ 42, №6 (2025)50451225122025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://journals.rcsi.science/0233-4755/article/view/362241

Coronaviruses, including the pandemic SARS-CoV-2, encode 16 non-structural proteins that regulate various stages of virus reproduction inside the infected cell but are not part of the virion structure. Some of these proteins are responsible for the formation of viroplasm, which is necessary for the reproduction of the viral genome. A characteristic feature of viroplasm is the formation of double-membrane vesicles, the physicochemical mechanisms of which are still unclear. At the same time, it is known that the non-structural protein 3 (nsp-3) plays an important role in this process. In this work, for the X macrodomain (X-domain) of the nsp-3 protein of SARS-CoV-2, we showed that it is capable of binding only to membranes containing acidic lipids. This domain forms various membrane tubulations, from filamentous to spherical, depending on the cholesterol content. Thus, X-domain of the nsp-3 protein of SARS-CoV-2 can be the initiator of the formation of double-membrane vesicles due to predominantly electrostatic interactions with membranes of cellular organelles.

Коронавирусы, в том числе пандемический вирус SARS-CoV-2, кодируют 16 неструктурных белков, регулирующих различные стадии воспроизводства вируса внутри инфицированной клетки, но не входящих в структуру вириона. Часть этих белков отвечает за формирование вироплазмы, ответственной за воспроизводство вирусного генома. Характерной особенностью вироплазмы является образование двумембранных везикул, физико-химические механизмы формирования которых до сих пор не ясны. При этом известно, что важную роль в данном процессе играет неструктурный белок (non-structural protein) nsp-3. В данной работе для макродомена X (X-домена) белка nsp-3 коронавируса SARS-CoV-2 мы показали, что он способен связываться только с мембранами, содержащими анионные липиды. В зависимости от содержания холестерина в составе мембраны данный домен способен образовывать различные мембранные выросты, от филаментозных до сферических. Таким образом, X-домен белка nsp-3 коронавируса SARS-CoV-2 может быть инициатором образования двумембранных везикул за счет преимущественно электростатических взаимодействий с мембранами клеточных органелл.

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