Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

Science
Matthias ThomsRoland Beckmann

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.

References

Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jan 5, 2005·PLoS Biology·Michael P RobertsonWilliam G Scott
Dec 13, 2005·Microbiology and Molecular Biology Reviews : MMBR·Susan R Weiss, Sonia Navas-Martin
Aug 1, 2006·Advances in Virus Research·Paul S Masters
Aug 17, 2006·FEMS Microbiology Reviews·Lia van der HoekBen Berkhout
Mar 7, 2009·Journal of Virology·Yukinobu TohyaShinji Makino
Oct 20, 2009·Nature Structural & Molecular Biology·Wataru KamitaniShinji Makino
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 27, 2010·Methods in Molecular Biology·Ajay SharmaRamanujan S Hegde
Nov 11, 2011·Journal of Virology·Konstantin M J SparrerKarl-Klaus Conzelmann
Feb 6, 2014·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Naoki MiyazawaNobuhiro Takahashi
Mar 22, 2015·Current Opinion in Microbiology·Konstantin M J Sparrer, Michaela U Gack
Aug 8, 2015·Nature·Alan BrownV Ramakrishnan
Aug 19, 2015·Journal of Structural Biology·Alexis Rohou, Nikolaus Grigorieff
Sep 8, 2015·Nature·Amedee des GeorgesYaser Hashem
Sep 19, 2015·Nucleic Acids Research·Sarah MatheislRoland Beckmann
Nov 26, 2015·Journal of Structural Biology·Kai Zhang
Jun 28, 2016·Nature Reviews. Microbiology·Emmie de WitVincent J Munster
Feb 7, 2017·Nature Methods·Ali PunjaniMarcus A Brubaker
Jun 6, 2017·Acta Crystallographica. Section D, Structural Biology·Tom BurnleyMartyn Winn
Jul 16, 2017·Protein Science : a Publication of the Protein Society·Thomas D GoddardThomas E Ferrin
Sep 6, 2017·Nature Microbiology·Konstantin M J SparrerMichaela U Gack
Jul 25, 2016·Diseases·Yvonne Xinyi LimDing Xiang Liu
Jun 8, 2018·Nature·Michael AmeismeierRoland Beckmann

❮ Previous
Next ❯

Citations

Aug 4, 2020·ELife·Niladri K SinhaRachel Green
Sep 11, 2020·Nature Structural & Molecular Biology·Katharina SchubertNenad Ban
Sep 26, 2020·Frontiers in Cell and Developmental Biology·Andres Mariano Alonso, Luis Diambra
Oct 11, 2020·Signal Transduction and Targeted Therapy·Kendra R VannTatiana G Kutateladze
Oct 21, 2020·Nature Reviews. Nephrology·Luca PericoGiuseppe Remuzzi
Oct 29, 2020·International Reviews of Immunology·Ashutosh KumarKamla Kant
Oct 22, 2020·Journal of Medical Virology·Ashutosh KumarKamla Kant
Nov 6, 2020·The Journal of General Virology·Zhou ShenGuiqing Peng
Nov 29, 2020·Expert Opinion on Therapeutic Patents·Clemente CapassoClaudiu T Supuran
Nov 26, 2020·Proteomics·Lucia Grenga, Jean Armengaud
Dec 2, 2020·Biochemical Society Transactions·Dene R LittlerBenjamin S Gully
Dec 3, 2020·Nucleic Acids Research·Sylvain de BreyneThéophile Ohlmann
Oct 31, 2020·Genome Biology and Evolution·Zhihua OuAntoine Danchin
Dec 15, 2020·Wellcome Open Research·Stefan BressonDavid Tollervey
Dec 19, 2020·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Hongjie Xia, Pei-Yong Shi
Jan 5, 2021·Human Vaccines & Immunotherapeutics·Firzan NainuHarapan Harapan
Nov 28, 2020·Journal of Molecular Biology·Rimanshee AryaMukesh Kumar
Oct 25, 2020·The Protein Journal·Mihaela Ileana Ionescu
Dec 16, 2020·IScience·Cameron SemperAlexei Savchenko
Jan 19, 2021·Journal of Basic Microbiology·Swapnil B KadamVitthal T Barvkar
Jan 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Christopher P LapointeJoseph D Puglisi
Jan 26, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Prem RajakSumedha Roy
Nov 26, 2020·Journal of Virology·Lauren K ClarkChad M Petit
Dec 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiao-Huan LiuTao Wang
Oct 6, 2020·IScience·Johannes BurtscherGrégoire P Millet
Jan 19, 2021·Biophysical Journal·Tristan I CrollJane S Richardson
Oct 30, 2020·Nature Reviews. Microbiology·Philip V'kovskiVolker Thiel
Feb 4, 2021·Nature Communications·Jerzy OsipiukAndrzej Joachimiak
Feb 8, 2021·Stem Cell Research·Gangyu SunZhizhi Wang
Feb 16, 2021·Frontiers in Molecular Biosciences·Shiv BharadwajSang Gu Kang
Nov 21, 2020·Nature Reviews. Immunology·Ronen AlonDavid J Topham
Jan 5, 2021·Frontiers in Molecular Biosciences·Giuseppina MarianoJulien R C Bergeron
Jan 23, 2021·Membranes·Jordana Muñoz-BasagoitiNuria Izquierdo-Useros
Dec 31, 2020·Pediatric Investigation·Fuyu Lin, Kunling Shen
Jan 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Leonardo LupacchiniPatrizia Russo
Feb 16, 2021·Frontiers in Immunology·Bing XieYou Shang

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
nuclear magnetic resonance
Enzyme-linked immunosorbent assay

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.