6lks
Effects of zinc ion on oligomerization and pH stability of influenza virus hemagglutinin
Structural highlights
FunctionA7LI25_9INFA Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore (By similarity).[RuleBase:RU003324][SAAS:SAAS001364_004_327643] Publication Abstract from PubMedDivalent cations Cu(2+) and Zn(2+) 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 Zn(2+) 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 Zn(2+) 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 Zn(2+). 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 Zn(2+) may facilitate the conformational changes of HA, analogous to that induced by acidic pH. Divalent cation-induced conformational changes of influenza virus hemagglutinin.,Seok JH, Kim H, Lee DB, An JS, Kim EJ, Lee JH, Chung MS, Kim KH Sci Rep. 2020 Sep 22;10(1):15457. doi: 10.1038/s41598-020-72368-x. PMID:32963316[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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