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Modulation of Cholesterol-Dependent Activity of Macrophages IC-21 by a Peptide Containing Two CRAC-Motifs from Protein M1 of Influenza Virusстатья
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 24 января 2020 г.
- Авторы: Dunina-Barkovskaya A.Ya, Vishnyakova Kh S., Baratova L.A., Radyukhin V.A.
- Журнал: Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology
- Том: 13
- Номер: 3
- Год издания: 2019
- Издательство: Pleiades Publishing, Ltd
- Местоположение издательства: Road Town, United Kingdom
- Первая страница: 268
- Последняя страница: 276
- Оригинальные версии: МОДУЛЯЦИЯ ХОЛЕСТЕРИН-ЗАВИСИМОЙ АКТИВНОСТИ МАКРОФАГОВ IC-21 ПЕПТИДОМ, СОДЕРЖАЩИМ ДВА CRAC-МОТИВА ИЗ БЕЛКА М1 ВИРУСА ГРИППА 2019 А.Я. Дунина-Барковская, Х.С. Вишнякова,Л.А. Баратова, В.А. Радюхин БИОЛОГИЧЕСКИЕ МЕМБРАНЫ, 2019, том 36, № 4, с. 271–280
- DOI: 10.1134/S1990747819030139
- Аннотация: Functioning of many membrane proteins is regulated by cholesterol. Some proteins were shown to contain cholesterol-recognizing amino-acid consensus (CRAC) motif. In particular, influenza virus protein M1 bears these motifs. To study functional roles and action mechanisms of peptides containing cholesterol-recognizing amino-acid consensus (CRAC) motifs, we designed and synthesized peptide RTKLWEMLVELGNMDKAVKLWRKLKR (peptide P4), which includes two peptides corresponding to CRAC-containing α-helices 3 and 6 of influenza virus protein M1 (LEVLMEWLKTR, aa 39–49, and NNMDKAVKLYRKLK, aa 91–105, respectively). We show that peptide P4 in a concentration range from 0.5 to 50 μM dose-dependently modulates cholesterol-dependent interactions of cultured macrophages IC-21 with 2-micron latex particles mimicking bacteria. The effect of peptide P4 was stronger than the effects of the composing peptides studied previously and exhibited a biphasic dose–response relationship. At concentrations from 0.5 to 10 μM peptide P4 significantly increased the number of cell-associated particles; at concentrations 10–20 μM the number of cell-associated particles decreased, and at concentrations 20–50 μM peptide P4 suppressed the cell activity and cell adhesion and produced a toxic effect. Upon extraction of membrane cholesterol by means of methyl-β-cyclodextrin the inhibitory effects of peptide P4 developed at much lower concentrations. The biphasic dose-dependence of the peptide P4 effect and the influence of methyl-β-cyclodextrin can be explained by the ability of peptide P4 to interact with membrane cholesterol. We suggest that peptide P4 at low concentrations facilitates the formation of cholesterol-enriched domains in plasma membrane and thus stimulates aggregation of cell receptors responsible for interactions of macrophages with particles. At higher concentrations peptide P4 may interfere with the activity of cholesterol-dependent receptors due to competitive binding of cholesterol and thus suppress both cell–particle and cell–substrate interactions. We believe that peptide P4 may serve as a useful tool for studies of cholesterol-dependent processes in cells and may serve a basis for the design of new antimicrobial and immunomodulating substances.
- Добавил в систему: Дунина-Барковская Антонина Яковлевна