Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses.
Devarkar, S.C., Vetick, M., Balaji, S., Lomakin, I.B., Yang, L., Jin, D., Gilbert, W.V., Chen, S., Xiong, Y.(2023) Cell Rep 42: 113156-113156
- PubMed: 37733586
- DOI: https://doi.org/10.1016/j.celrep.2023.113156
- Primary Citation of Related Structures:
8T4S - PubMed Abstract:
All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most distantly related member to SARS-CoV-2, and the mechanism for host translation inhibition by MERS-CoV Nsp1 remains controversial. Herein, we show that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit. Using cryogenic electron microscopy (cryo-EM), we report a 2.6-Å structure of the MERS-CoV Nsp1 bound to the human 40S ribosomal subunit. The extensive interactions between C-terminal domain of MERS-CoV Nsp1 and the mRNA entry channel of the 40S ribosomal subunit are critical for its translation inhibition function. This mechanism of MERS-CoV Nsp1 is strikingly similar to SARS-CoV and SARS-CoV-2 Nsp1, despite modest sequence conservation. Our results reveal that the mechanism of host translation inhibition is conserved across β-CoVs and highlight a potential therapeutic target for the development of antivirals that broadly restrict β-CoVs.
Organizational Affiliation:
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.