7k3g

Publication Abstract from PubMed

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-A 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 alpha-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.

Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers.,Mandala VS, McKay MJ, Shcherbakov AA, Dregni AJ, Kolocouris A, Hong M Nat Struct Mol Biol. 2020 Nov 11. pii: 10.1038/s41594-020-00536-8. doi:, 10.1038/s41594-020-00536-8. PMID:33177698^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.