Transmembrane conformation of the envelope protein of an alpha coronavirus, NL63

Citations Over TimeTop 12% of 2024 papers

Abstract

The envelope (E) proteins of coronaviruses (CoVs) form cation-conducting channels that are associated with the pathogenicity of these viruses. To date, high-resolution structural information about these viroporins is limited to the SARS-CoV E protein. To broaden our structural knowledge of other members of this family of viroporins, we now investigate the conformation of the E protein of the human coronavirus (hCoV), NL63. Using two- and three-dimensional magic-angle-spinning NMR, we have measured 13 C and 15 N chemical shifts of the transmembrane domain of E (ETM), which yielded backbone (ϕ, ψ) torsion angles. We further measured the water accessibility of NL63 ETM at neutral pH versus acidic pH in the presence of Ca2+ ions. These data show that NL63 ETM adopts a regular α-helical conformation that is unaffected by pH and the N-terminal ectodomain. Interestingly, the water accessibility of NL63 ETM increases only modestly at acidic pH in the presence of Ca2+ compared to neutral pH, in contrast to SARS ETM, which becomes much more hydrated at acidic pH. This difference suggests a structural basis for the weaker channel conductance of α-CoV compared to β-CoV E proteins. The weaker E channel activity may in turn contribute to the reduced virulence of hCoV-NL63 compared to SARS-CoV viruses.

Related Papers

• → Role of the Juxtamembrane Domains of the Transforming Growth Factor-α Precursor and the β-Amyloid Precursor Protein in Regulated Ectodomain Shedding(1997)132 cited
• → Isolated Toll-like Receptor Transmembrane Domains Are Capable of Oligomerization(2012)78 cited
• → A mutational study of transmembrane helix–helix interactions(2007)20 cited
• → Sequence of the SARS-CoV-2 spike transmembrane domain makes it inherently dynamic(2021)1 cited