Unknown

Dataset Information

0

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


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.

SUBMITTER: Mandala VS 

PROVIDER: S-EPMC7718435 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7523133 | biostudies-literature
| S-EPMC9851921 | biostudies-literature
| S-EPMC5405556 | biostudies-literature
| EMPIAR-11067 | biostudies-other
| S-EPMC2997931 | biostudies-literature
| S-EPMC7194921 | biostudies-literature
| S-EPMC5459333 | biostudies-literature
2014-10-31 | E-GEOD-52920 | biostudies-arrayexpress
| S-EPMC10186300 | biostudies-literature
| S-EPMC7557813 | biostudies-literature