8T4S

MERS-CoV Nsp1 protein bound to the Human 40S Ribosomal subunit

Summary for 8T4S

• Entry DOI: 10.2210/pdb8t4s/pdb
• EMDB information: 41039 41063 41064 41065
• Descriptor: 18S rRNA, 40S ribosomal protein S8, 40S ribosomal protein S9, ... (39 entities in total)
• Functional Keywords: mers-cov nsp1, translation inhibition, 40s ribosome, betacoronaviruses, ribosome, ribosome-viral protein complex, ribosome/viral protein
• Biological source: Middle East respiratory syndrome-related coronavirus; More
• Total number of polymer chains: 36
• Total formula weight: 1257354.76

Authors

Devarkar, S.C.,Xiong, Y. (deposition date: 2023-06-09, release date: 2023-10-04, Last modification date: 2023-10-11)

Primary citation

Devarkar, S.C.,Vetick, M.,Balaji, S.,Lomakin, I.B.,Yang, L.,Jin, D.,Gilbert, W.V.,Chen, S.,Xiong, Y.
Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses.
Cell Rep, 42:113156-113156, 2023

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.

PubMed: 37733586
DOI: 10.1016/j.celrep.2023.113156

Experimental method

ELECTRON MICROSCOPY (2.6 Å)