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Structure paper

タイトル	Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.
ジャーナル・号・ページ	Science, Vol. 369, Issue 6508, Page 1249-1255, Year 2020
掲載日	2020年9月4日
著者	Matthias Thoms / Robert Buschauer / Michael Ameismeier / Lennart Koepke / Timo Denk / Maximilian Hirschenberger / Hanna Kratzat / Manuel Hayn / Timur Mackens-Kiani / Jingdong Cheng / Jan H Straub / Christina M Stürzel / Thomas Fröhlich / Otto Berninghausen / Thomas Becker / Frank Kirchhoff / Konstantin M J Sparrer / Roland Beckmann /
PubMed 要旨	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 ...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 40 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 Nsp1-40 and various native Nsp1-40 and -80 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.
リンク	Science / PubMed:32680882 / PubMed Central
手法	EM (単粒子)
解像度	2.6 - 3.2 Å
構造データ	11276 6zlw EMDB-11276, PDB-6zlw: SARS-CoV-2 Nsp1 bound to the human 40S ribosomal subunit 手法: EM (単粒子) / 解像度: 2.6 Å 11288 6zm7 EMDB-11288, PDB-6zm7: SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-EBP1 ribosome complex 手法: EM (単粒子) / 解像度: 2.7 Å 11289 6zme EMDB-11289, PDB-6zme: SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-eERF1 ribosome complex 手法: EM (単粒子) / 解像度: 3.0 Å 11292 6zmi EMDB-11292, PDB-6zmi: SARS-CoV-2 Nsp1 bound to the human LYAR-80S ribosome complex 手法: EM (単粒子) / 解像度: 2.6 Å 11299 6zmo EMDB-11299, PDB-6zmo: SARS-CoV-2 Nsp1 bound to the human LYAR-80S-eEF1a ribosome complex 手法: EM (単粒子) / 解像度: 3.1 Å 11301 6zmt EMDB-11301, PDB-6zmt: SARS-CoV-2 Nsp1 bound to a pre-40S-like ribosome complex 手法: EM (単粒子) / 解像度: 3.0 Å 11310 6zn5 EMDB-11310, PDB-6zn5: SARS-CoV-2 Nsp1 bound to a pre-40S-like ribosome complex - state 2 手法: EM (単粒子) / 解像度: 3.2 Å 11325 6zon EMDB-11325, PDB-6zon: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex - state 1 手法: EM (単粒子) / 解像度: 3.0 Å 11335 6zp4 EMDB-11335, PDB-6zp4: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex - state 2 手法: EM (単粒子) / 解像度: 2.9 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-SF4: IRON/SULFUR CLUSTER ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP / GTP, エネルギー貯蔵分子YM
由来	homo sapiens (ヒト) severe acute respiratory syndrome coronavirus 2 (ウイルス)
キーワード	VIRAL PROTEIN / Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome