4.7 Article

Divalent cation-induced conformational changes of influenza virus hemagglutinin

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SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-020-72368-x

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  1. Korea Drug Development Fund - Ministry of Science and ICT
  2. Ministry of Trade, Industry, and Energy
  3. Ministry of Health and Welfare [KDDF-201712-14]
  4. [NRF-2016R1E1A1A01942558]

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Divalent cations Cu2+ and Zn2+ can prevent the viral growth in mammalian cells during influenza infection, and viral titers decrease significantly on a copper surface. The underlying mechanisms include DNA damage by radicals, modulation of viral protease, M1 or neuraminidase, and morphological changes in viral particles. However, the molecular mechanisms underlying divalent cation-mediated antiviral activities are unclear. An unexpected observation of this study was that a Zn2+ ion is bound by Glu68 and His137 residues at the head regions of two neighboring trimers in the crystal structure of hemagglutinin (HA) derived from A/Thailand/CU44/2006. The binding of Zn2+ at high concentrations induced multimerization of HA and decreased its acid stability. The acid-induced conformational change of HA occurred even at neutral pH in the presence of Zn2+. The fusion of viral and host endosomal membranes requires substantial conformational changes in HA upon exposure to acidic pH. Therefore, our results suggest that binding of Zn2+ may facilitate the conformational changes of HA, analogous to that induced by acidic pH.

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