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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-11301 | ||||||||||||
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Title | SARS-CoV-2 Nsp1 bound to a pre-40S-like ribosome complex | ||||||||||||
![]() | SARS-CoV-2 Nsp1 bound to a pre-40S-like ribosome complex | ||||||||||||
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![]() | Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome / VIRAL PROTEIN | ||||||||||||
Function / homology | ![]() endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage ...endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / IRE1-RACK1-PP2A complex / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / U3 snoRNA binding / protein kinase A binding / Translation initiation complex formation / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / preribosome, small subunit precursor / pigmentation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of cell division / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Peptide chain elongation / monocyte chemotaxis / Selenocysteine synthesis / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / Formation of a pool of free 40S subunits / phagocytic cup / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / TOR signaling / T cell proliferation involved in immune response / Major pathway of rRNA processing in the nucleolus and cytosol / spindle assembly / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of translational fidelity / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / ribosomal small subunit export from nucleus / erythrocyte development / translation regulator activity / Protein methylation / Nuclear events stimulated by ALK signaling in cancer / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / cytosolic ribosome / positive regulation of cell cycle / signaling adaptor activity / negative regulation of smoothened signaling pathway / stress granule assembly / positive regulation of intrinsic apoptotic signaling pathway / Mitotic Prometaphase / laminin binding / rough endoplasmic reticulum / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / EML4 and NUDC in mitotic spindle formation / Maturation of protein E / positive regulation of JUN kinase activity / Maturation of protein E Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | ||||||||||||
![]() | Thoms M / Buschauer R | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Authors: Matthias Thoms / Robert Buschauer / Michael Ameismeier / Lennart Koepke / Timo Denk / Maximilian Hirschenberger / Hanna Kratzat / Manuel Hayn / Timur Mackens-Kiani / Jingdong Cheng / Jan H ...Authors: 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 / ![]() 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 ...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. | ||||||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 97.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 52.3 KB 52.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12.8 KB | Display | ![]() |
Images | ![]() | 33.7 KB | ||
Filedesc metadata | ![]() | 11.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 468.3 KB | Display | ![]() |
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Full document | ![]() | 467.8 KB | Display | |
Data in XML | ![]() | 13.2 KB | Display | |
Data in CIF | ![]() | 17.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6zmtMC ![]() 6zlwC ![]() 6zm7C ![]() 6zmeC ![]() 6zmiC ![]() 6zmoC ![]() 6zn5C ![]() 6zonC ![]() 6zp4C C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | SARS-CoV-2 Nsp1 bound to a pre-40S-like ribosome complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.059 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : SARS-CoV-2 Nsp1 bound to a pre-40S-like ribosome complex
+Supramolecule #1: SARS-CoV-2 Nsp1 bound to a pre-40S-like ribosome complex
+Supramolecule #2: Pre-40S-like ribosome complex
+Supramolecule #3: SARS-CoV-2 Nsp1
+Macromolecule #1: 40S ribosomal protein SA
+Macromolecule #2: 40S ribosomal protein S3a
+Macromolecule #3: 40S ribosomal protein S2
+Macromolecule #4: 40S ribosomal protein S4, X isoform
+Macromolecule #5: 40S ribosomal protein S3
+Macromolecule #6: 40S ribosomal protein S6
+Macromolecule #7: 40S ribosomal protein S7
+Macromolecule #8: 40S ribosomal protein S8
+Macromolecule #9: 40S ribosomal protein S9
+Macromolecule #10: 40S ribosomal protein S5
+Macromolecule #11: 40S ribosomal protein S11
+Macromolecule #12: 40S ribosomal protein S10
+Macromolecule #13: 40S ribosomal protein S13
+Macromolecule #14: 40S ribosomal protein S12
+Macromolecule #15: 40S ribosomal protein S14
+Macromolecule #16: 40S ribosomal protein S15
+Macromolecule #17: 40S ribosomal protein S16
+Macromolecule #18: 40S ribosomal protein S17
+Macromolecule #19: 40S ribosomal protein S18
+Macromolecule #20: 40S ribosomal protein S19
+Macromolecule #21: 40S ribosomal protein S20
+Macromolecule #22: 40S ribosomal protein S15a
+Macromolecule #23: 40S ribosomal protein S23
+Macromolecule #24: 40S ribosomal protein S24
+Macromolecule #25: 40S ribosomal protein S21
+Macromolecule #26: 40S ribosomal protein S25
+Macromolecule #27: 40S ribosomal protein S27
+Macromolecule #28: 40S ribosomal protein S28
+Macromolecule #29: 40S ribosomal protein S30
+Macromolecule #30: 40S ribosomal protein S29
+Macromolecule #31: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #32: Receptor of activated protein C kinase 1
+Macromolecule #34: Non-structural protein 1
+Macromolecule #35: Pre-rRNA-processing protein TSR1 homolog
+Macromolecule #33: 18S ribosomal RNA
+Macromolecule #36: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 44.8 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |