Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers.
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.
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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