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TitleStructural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses.
Journal, issue, pagesCell Rep, Vol. 42, Issue 10, Page 113156, Year 2023
Publish dateSep 19, 2023
AuthorsSwapnil C Devarkar / Michael Vetick / Shravani Balaji / Ivan B Lomakin / Luojia Yang / Danni Jin / Wendy V Gilbert / Sidi Chen / Yong Xiong /
PubMed AbstractAll 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 ...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.
External linksCell Rep / PubMed:37733586
MethodsEM (single particle)
Resolution2.6 Å
Structure data

EMDB-41039, PDB-8t4s:
MERS-CoV Nsp1 protein bound to the Human 40S Ribosomal subunit
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-41063: MERS-CoV Nsp1 protein binds the human 40S ribosome - Consensus Reconstruction
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-41064: MERS-CoV Nsp1 protein bound to the human 40S ribosome: Focus Refined 40S Head Map
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-41065: MERS-CoV Nsp1 protein bound to human 40S ribosome: 40S Body Focus Refined Map
Method: EM (single particle) / Resolution: 2.6 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • middle east respiratory syndrome-related coronavirus
KeywordsRibosome/Viral Protein / MERS-CoV Nsp1 / translation inhibition / 40S ribosome / betacoronaviruses / RIBOSOME / Ribosome-Viral Protein complex

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