EMD-11299

Single-particle
3.1 Å
EMD-11299 Deposition: 03/07/2020
Map released: 19/08/2020
Last modified: 01/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-11299

SARS-CoV-2 Nsp1 bound to the human LYAR-80S-eEF1a ribosome complex

EMD-11299

Single-particle
3.1 Å
EMD-11299 Deposition: 03/07/2020
Map released: 19/08/2020
Last modified: 01/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 Nsp1 bound to the human LYAR-80S-eEF1a ribosome complex
Fitted models: 6zmo (Avg. Q-score: 0.519)

Deposition Authors: Thoms M , Buschauer R
Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.
PUBMED: 32680882
DOI: doi:10.1126/science.abc8665
ISSN: 1095-9203
ASTM: SCIEAS
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.