EMD-11276
SARS-CoV-2 Nsp1 bound to the human 40S ribosomal subunit
EMD-11276
Single-particle2.6 Å
![EMD-11276](https://www.ebi.ac.uk/emdb/images/entry/EMD-11276/400_11276.gif)
Map released: 29/07/2020
Last modified: 01/05/2024
Sample Organism:
Homo sapiens,
Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 Nsp1 bound to the human 40S ribosomal subunit
Fitted models: 6zlw (Avg. Q-score: 0.595)
Deposition Authors: Thoms M
,
Buschauer R
Sample: SARS-CoV-2 Nsp1 bound to the human 40S ribosomal subunit
Fitted models: 6zlw (Avg. Q-score: 0.595)
Deposition Authors: Thoms M
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Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.
Thoms M
,
Buschauer R
,
Ameismeier M
,
Koepke L
,
Denk T
,
Hirschenberger M
,
Kratzat H
,
Hayn M,
Mackens-Kiani T
,
Cheng J
,
Straub JH,
Sturzel CM,
Frohlich T
,
Berninghausen O
,
Becker T
,
Kirchhoff F
,
Sparrer KMJ
,
Beckmann R
(2020) Science , 369 , 1249 - 1255
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(2020) Science , 369 , 1249 - 1255
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1), which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40S ribosomal subunit, resulting in shutdown of messenger RNA (mRNA) translation both in vitro and in cells. Structural analysis by cryo-electron microscopy of in vitro-reconstituted Nsp1-40S and various native Nsp1-40S and -80S complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks retinoic acid-inducible gene I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1), which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40S ribosomal subunit, resulting in shutdown of messenger RNA (mRNA) translation both in vitro and in cells. Structural analysis by cryo-electron microscopy of in vitro-reconstituted Nsp1-40S and various native Nsp1-40S and -80S complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks retinoic acid-inducible gene I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.