Amphipathic CRAC-Containing Peptides Derived from the Influenza Virus A M1 Protein Modulate Cholesterol-Dependent Activity of Cultured IC-21 Macrophages
- Авторы: Dunina-Barkovskaya A.1, Vishnyakova K.2, Golovko A.3, Arutyunyan A.1, Baratova L.1, Bathishchev O.4, Radyukhin V.1
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Учреждения:
- Belozersky Institute of Physico-Chemical Biology
- Engelhardt Institute of Molecular Biology
- Faculty of Bioengineering and Bioinformatics
- Frumkin Institute of Physical Chemistry and Electrochemistry
- Выпуск: Том 83, № 8 (2018)
- Страницы: 982-991
- Раздел: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151703
- DOI: https://doi.org/10.1134/S0006297918080096
- ID: 151703
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Аннотация
Entry of many viral and bacterial pathogens into host cells depends on cholesterol and/or cholesterol-enriched domains (lipid rafts) in the cell membrane. Earlier, we showed that influenza virus A matrix protein M1 contains amphipathic α-helices with exposed cholesterol-recognizing amino acid consensus (CRAC) motifs. In order to test possible functional activity of these motifs, we studied the effects of three synthetic peptides corresponding to the CRAC-containing α-helices of the viral M1 protein on the phagocytic activity of cultured mouse IC-21 macrophages. The following peptides were used: LEVLMEWLKTR (M1 α-helix 3, a.a. 39–49; further referred to as peptide 1), NNMDKAVKLYRKLK (M1 α-helix 6, a.a. 91–105; peptide 2), and GLKNDLLENLQAYQKR (M1 α-helix 13, a.a. 228–243; peptide 3). We found that all three peptides modulated interactions of IC-21 macrophages with non-opsonized 2-μm target particles. The greatest effect was demonstrated by peptide 2: in the presence of 35 μM peptide 2, the phagocytic index of IC-21 macrophages exceeded the control value by 60%; 10–11 mM methyl-β-cyclodextrin abolished this effect. Peptides 1 and 3 exerted weak inhibitory effect in a narrow concentration range of 5–10 μM. The dose-response curves could be approximated by a sum of two (stimulatory and inhibitory) components with different Hill coefficients, suggesting existence of at least two peptide-binding sites with different affinities on the cell surface. CD spectroscopy confirmed that the peptides exhibit structural flexibility in solutions. Altogether, our data indicate that amphipathic CRAC-containing peptides derived from the viral M1 protein modulate lipid raft-dependent processes in IC-21 macrophages.
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Об авторах
A. Dunina-Barkovskaya
Belozersky Institute of Physico-Chemical Biology
Автор, ответственный за переписку.
Email: dunina.aya@gmail.com
Россия, Moscow, 119991
Kh. Vishnyakova
Engelhardt Institute of Molecular Biology
Email: varvic@belozersky.msu.ru
Россия, Moscow, 119991
A. Golovko
Faculty of Bioengineering and Bioinformatics
Email: varvic@belozersky.msu.ru
Россия, Moscow, 119991
A. Arutyunyan
Belozersky Institute of Physico-Chemical Biology
Email: varvic@belozersky.msu.ru
Россия, Moscow, 119991
L. Baratova
Belozersky Institute of Physico-Chemical Biology
Email: varvic@belozersky.msu.ru
Россия, Moscow, 119991
O. Bathishchev
Frumkin Institute of Physical Chemistry and Electrochemistry
Email: varvic@belozersky.msu.ru
Россия, Moscow, 119071
V. Radyukhin
Belozersky Institute of Physico-Chemical Biology
Автор, ответственный за переписку.
Email: varvic@belozersky.msu.ru
Россия, Moscow, 119991