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Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers.
Mandala, Venkata S; McKay, Matthew J; Shcherbakov, Alexander A; Dregni, Aurelio J; Kolocouris, Antonios; Hong, Mei.
  • Mandala VS; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • McKay MJ; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Shcherbakov AA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Dregni AJ; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Kolocouris A; Department of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, Athens, Greece.
  • Hong M; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. meihong@mit.edu.
Nat Struct Mol Biol ; 27(12): 1202-1208, 2020 12.
Article in English | MEDLINE | ID: covidwho-1387444
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Envelope Proteins / SARS-CoV-2 / Lipid Bilayers Language: English Journal: Nat Struct Mol Biol Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: S41594-020-00536-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Envelope Proteins / SARS-CoV-2 / Lipid Bilayers Language: English Journal: Nat Struct Mol Biol Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: S41594-020-00536-8