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dc.contributor.authorMandala, Venkata S
dc.contributor.authorMcKay, Matthew J
dc.contributor.authorShcherbakov, Alexander A
dc.contributor.authorDregni, Aurelio J
dc.contributor.authorKolocouris, Antonios
dc.contributor.authorHong, Mei
dc.date.accessioned2022-03-08T20:31:03Z
dc.date.available2022-03-08T20:31:03Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/1721.1/141070
dc.description.abstractAn essential protein of the SARS-CoV-2 virus, the envelope protein E, forms a homopentameric cation channel that is important for virus pathogenicity. Here we report a 2.1-Å structure and the drug-binding site of E’s transmembrane domain (ETM), determined using solid-state NMR spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum–Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow pore. The protein deviates from the ideal α-helical geometry due to three phenylalanine residues, which stack within each helix and between helices. Together with valine and leucine interdigitation, these cause a dehydrated pore compared with the viroporins of influenza viruses and HIV. Hexamethylene amiloride binds the polar amino-terminal lumen, whereas acidic pH affects the carboxy-terminal conformation. Thus, the N- and C-terminal halves of this bipartite channel may interact with other viral and host proteins semi-independently. The structure sets the stage for designing E inhibitors as antiviral drugs.en_US
dc.language.isoen
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.isversionof10.1038/S41594-020-00536-8en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleStructure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayersen_US
dc.typeArticleen_US
dc.identifier.citationMandala, Venkata S, McKay, Matthew J, Shcherbakov, Alexander A, Dregni, Aurelio J, Kolocouris, Antonios et al. 2020. "Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers." Nature Structural and Molecular Biology, 27 (12).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry
dc.relation.journalNature Structural and Molecular Biologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2022-03-08T20:28:07Z
dspace.orderedauthorsMandala, VS; McKay, MJ; Shcherbakov, AA; Dregni, AJ; Kolocouris, A; Hong, Men_US
dspace.date.submission2022-03-08T20:28:09Z
mit.journal.volume27en_US
mit.journal.issue12en_US
mit.licensePUBLISHER_POLICY
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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