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Amphipathic CRAC-Containing Peptides Derived from the Influenza Virus A M1 Protein Modulate Cholesterol-Dependent Activity of Cultured IC-21 Macrophages

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An Erratum to this article was published on 17 September 2018

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Abstract

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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  • 17 September 2018

    On p. 982 in the list of authors instead of:

    O. V. Bathishchev

    Should read:

    O. V. Batishchev

Abbreviations

CD:

circular dichroism

CRAC:

cholesterol-recognizing amino acid consensus

mβCD:

methyl-β-cyclodextrin

MM :

molecular mass

TFE:

trifluoroethanol

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Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    A. Ya. Dunina-Barkovskaya, A. M. Arutyunyan, L. A. Baratova & V. A. Radyukhin

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    Kh. S. Vishnyakova

  3. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991, Moscow, Russia

    A. O. Golovko

  4. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 119071, Moscow, Russia

    O. V. Bathishchev

Authors
  1. A. Ya. Dunina-Barkovskaya
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  2. Kh. S. Vishnyakova
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  3. A. O. Golovko
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  4. A. M. Arutyunyan
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  5. L. A. Baratova
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  6. O. V. Bathishchev
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  7. V. A. Radyukhin
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Corresponding authors

Correspondence to A. Ya. Dunina-Barkovskaya or V. A. Radyukhin.

Additional information

Published in Russian in Biokhimiya, 2018, Vol. 83, No. 8, pp. 1235–1246.

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Dunina-Barkovskaya, A.Y., Vishnyakova, K.S., Golovko, A.O. et al. Amphipathic CRAC-Containing Peptides Derived from the Influenza Virus A M1 Protein Modulate Cholesterol-Dependent Activity of Cultured IC-21 Macrophages. Biochemistry Moscow 83, 982–991 (2018). https://doi.org/10.1134/S0006297918080096

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  • DOI: https://doi.org/10.1134/S0006297918080096

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