SARS-CoV-2 Envelope Protein Forms Clustered Pentamers in Lipid Bilayers.
Noah H SombergWestley W WuJoão Medeiros-SilvaAurelio J DregniHyunil JoWilliam F DeGradoMei HongPublished in: Biochemistry (2022)
The SARS-CoV-2 envelope (E) protein is a viroporin associated with the acute respiratory symptoms of COVID-19. E forms cation-selective ion channels that assemble in the lipid membrane of the endoplasmic reticulum Golgi intermediate compartment. The channel activity of E is linked to the inflammatory response of the host cell to the virus. Like many viroporins, E is thought to oligomerize with a well-defined stoichiometry. However, attempts to determine the E stoichiometry have led to inconclusive results and suggested mixtures of oligomers whose exact nature might vary with the detergent used. Here, we employ 19 F solid-state nuclear magnetic resonance and the centerband-only detection of exchange (CODEX) technique to determine the oligomeric number of E's transmembrane domain (ETM) in lipid bilayers. The CODEX equilibrium value, which corresponds to the inverse of the oligomeric number, indicates that ETM assembles into pentamers in lipid bilayers, without any detectable fraction of low-molecular-weight oligomers. Unexpectedly, at high peptide concentrations and in the presence of the lipid phosphatidylinositol, the CODEX data indicate that more than five 19 F spins are within a detectable distance of about 2 nm, suggesting that the ETM pentamers cluster in the lipid bilayer. Monte Carlo simulations that take into account peptide-peptide and peptide-lipid interactions yielded pentamer clusters that reproduced the CODEX data. This supramolecular organization is likely important for E-mediated virus assembly and budding and for the channel function of the protein.
Keyphrases
- sars cov
- magnetic resonance
- fatty acid
- inflammatory response
- endoplasmic reticulum
- molecular dynamics simulations
- monte carlo
- solid state
- respiratory syndrome coronavirus
- magnetic resonance imaging
- electronic health record
- stem cells
- amino acid
- ionic liquid
- small molecule
- lipopolysaccharide induced
- respiratory failure
- toll like receptor
- bone marrow
- intensive care unit
- extracorporeal membrane oxygenation
- data analysis