dc.contributor.author | Mandala, Venkata S | |
dc.contributor.author | McKay, Matthew J | |
dc.contributor.author | Shcherbakov, Alexander A | |
dc.contributor.author | Dregni, Aurelio J | |
dc.contributor.author | Kolocouris, Antonios | |
dc.contributor.author | Hong, Mei | |
dc.date.accessioned | 2022-03-08T20:31:03Z | |
dc.date.available | 2022-03-08T20:31:03Z | |
dc.date.issued | 2020 | |
dc.identifier.uri | https://hdl.handle.net/1721.1/141070 | |
dc.description.abstract | An 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.iso | en | |
dc.publisher | Springer Science and Business Media LLC | en_US |
dc.relation.isversionof | 10.1038/S41594-020-00536-8 | en_US |
dc.rights | Article 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.source | PMC | en_US |
dc.title | Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Mandala, 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.department | Massachusetts Institute of Technology. Department of Chemistry | |
dc.relation.journal | Nature Structural and Molecular Biology | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2022-03-08T20:28:07Z | |
dspace.orderedauthors | Mandala, VS; McKay, MJ; Shcherbakov, AA; Dregni, AJ; Kolocouris, A; Hong, M | en_US |
dspace.date.submission | 2022-03-08T20:28:09Z | |
mit.journal.volume | 27 | en_US |
mit.journal.issue | 12 | en_US |
mit.license | PUBLISHER_POLICY | |
mit.metadata.status | Authority Work and Publication Information Needed | en_US |