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Structure paper

TitleSARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 10, Page 959-966, Year 2020
Publish dateSep 9, 2020
AuthorsKatharina Schubert / Evangelos D Karousis / Ahmad Jomaa / Alain Scaiola / Blanca Echeverria / Lukas-Adrian Gurzeler / Marc Leibundgut / Volker Thiel / Oliver Mühlemann / Nenad Ban /
PubMed AbstractThe SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show ...The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome. The protein inserts its C-terminal domain into the mRNA channel, where it interferes with mRNA binding. We observe translation inhibition in the presence of Nsp1 in an in vitro translation system and in human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5' untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines global inhibition of translation by Nsp1 with efficient translation of the viral mRNA to allow expression of viral genes.
External linksNat Struct Mol Biol / PubMed:32908316
MethodsEM (single particle)
Resolution2.5 - 4.1 Å
Structure data

11320

6zoj

EMDB-11320, PDB-6zoj:
SARS-CoV-2-Nsp1-40S complex, composite map
Method: EM (single particle) / Resolution: 2.8 Å

11321

6zok

EMDB-11321, PDB-6zok:
SARS-CoV-2-Nsp1-40S complex, focused on body
Method: EM (single particle) / Resolution: 2.8 Å

11322

6zol

EMDB-11322, PDB-6zol:
SARS-CoV-2-Nsp1-40S complex, focused on head
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-11323:
SARS-CoV-2-Nsp1 bound to 43S Pre-initiation complex
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-11609:
SARS-CoV-2-Nsp1 bound to a translationally inactive 80S ribosome
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
  • Human (human)
KeywordsTRANSLATION / inhibitor / mRNA channel / 40S ribosomal subunit

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