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Yorodumi- EMDB-11335: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome compl... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11335 | ||||||||||||
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Title | SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex - state 2 | ||||||||||||
Map data | SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex | ||||||||||||
Sample |
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Keywords | Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome / VIRAL PROTEIN | ||||||||||||
Function / homology | Function and homology information male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / positive regulation of mRNA cis splicing, via spliceosome / HRI-mediated signaling / response to kainic acid / Cellular response to mitochondrial stress / viral translational termination-reinitiation ...male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / positive regulation of mRNA cis splicing, via spliceosome / HRI-mediated signaling / response to kainic acid / Cellular response to mitochondrial stress / viral translational termination-reinitiation / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / negative regulation of translational initiation in response to stress / eukaryotic translation initiation factor 3 complex, eIF3e / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / PERK-mediated unfolded protein response / methionyl-initiator methionine tRNA binding / PERK regulates gene expression / IRES-dependent viral translational initiation / regulation of translational initiation in response to stress / translation reinitiation / eukaryotic translation initiation factor 2 complex / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / multi-eIF complex / cytoplasmic translational initiation / translation factor activity, RNA binding / mRNA cap binding / protein-synthesizing GTPase / eukaryotic 43S preinitiation complex / formation of translation preinitiation complex / : / 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 / eukaryotic 48S preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / metal-dependent deubiquitinase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / oxidized purine DNA binding / NF-kappaB complex / neural crest cell differentiation / ubiquitin-like protein conjugating enzyme binding / regulation of translational initiation / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / laminin receptor activity / pigmentation / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / iron-sulfur cluster binding / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / regulation of cell division / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / cysteine-type endopeptidase activator activity involved in apoptotic process / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / negative regulation of respiratory burst involved in inflammatory response Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||||||||
Authors | Thoms M / Buschauer R | ||||||||||||
Funding support | Germany, 3 items
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Citation | Journal: Science / Year: 2020 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
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_11335.map.gz | 96.1 MB | EMDB map data format | |
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Header (meta data) | emd-11335-v30.xml emd-11335.xml | 78.8 KB 78.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11335_fsc.xml | 12.7 KB | Display | FSC data file |
Images | emd_11335.png | 40 KB | ||
Filedesc metadata | emd-11335.cif.gz | 16.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11335 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11335 | HTTPS FTP |
-Validation report
Summary document | emd_11335_validation.pdf.gz | 494 KB | Display | EMDB validaton report |
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Full document | emd_11335_full_validation.pdf.gz | 493.6 KB | Display | |
Data in XML | emd_11335_validation.xml.gz | 13.2 KB | Display | |
Data in CIF | emd_11335_validation.cif.gz | 17.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11335 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11335 | HTTPS FTP |
-Related structure data
Related structure data | 6zp4MC 6zlwC 6zm7C 6zmeC 6zmiC 6zmoC 6zmtC 6zn5C 6zonC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_11335.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-Sample components
+Entire : SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome compl...
+Supramolecule #1: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome compl...
+Supramolecule #2: human 43S preinitiation ribosome complex - state 2
+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 S26
+Macromolecule #5: 40S ribosomal protein S4, X isoform
+Macromolecule #6: 60S ribosomal protein L41
+Macromolecule #7: 40S ribosomal protein S6
+Macromolecule #8: 40S ribosomal protein S7
+Macromolecule #9: 40S ribosomal protein S8
+Macromolecule #10: 40S ribosomal protein S9
+Macromolecule #11: 40S ribosomal protein S11
+Macromolecule #12: 40S ribosomal protein S13
+Macromolecule #13: 40S ribosomal protein S21
+Macromolecule #14: 40S ribosomal protein S15a
+Macromolecule #15: 40S ribosomal protein S24
+Macromolecule #16: 40S ribosomal protein S27
+Macromolecule #17: 40S ribosomal protein S30
+Macromolecule #19: 40S ribosomal protein S17
+Macromolecule #20: 40S ribosomal protein S3
+Macromolecule #21: 40S ribosomal protein S5
+Macromolecule #22: 40S ribosomal protein S10
+Macromolecule #23: 40S ribosomal protein S12
+Macromolecule #24: 40S ribosomal protein S15
+Macromolecule #25: 40S ribosomal protein S16
+Macromolecule #26: 40S ribosomal protein S18
+Macromolecule #27: 40S ribosomal protein S19
+Macromolecule #28: 40S ribosomal protein S20
+Macromolecule #29: 40S ribosomal protein S25
+Macromolecule #30: 40S ribosomal protein S28
+Macromolecule #31: 40S ribosomal protein S29
+Macromolecule #32: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #33: Receptor of activated protein C kinase 1
+Macromolecule #34: 40S ribosomal protein S14
+Macromolecule #35: 40S ribosomal protein S23
+Macromolecule #36: Eukaryotic translation initiation factor 1A, X-chromosomal
+Macromolecule #37: Eukaryotic translation initiation factor 3 subunit I
+Macromolecule #38: Eukaryotic translation initiation factor 3 subunit B
+Macromolecule #39: Eukaryotic translation initiation factor 3 subunit A
+Macromolecule #40: Eukaryotic translation initiation factor 3 subunit C
+Macromolecule #41: Eukaryotic translation initiation factor 3 subunit E
+Macromolecule #42: Eukaryotic translation initiation factor 3 subunit F
+Macromolecule #43: Eukaryotic translation initiation factor 3 subunit H
+Macromolecule #44: Eukaryotic translation initiation factor 3 subunit K
+Macromolecule #45: Eukaryotic translation initiation factor 3 subunit L
+Macromolecule #46: Eukaryotic translation initiation factor 3 subunit M
+Macromolecule #47: Eukaryotic translation initiation factor 3 subunit D
+Macromolecule #48: Unknown factor
+Macromolecule #50: Eukaryotic translation initiation factor 2 subunit 2
+Macromolecule #51: Eukaryotic translation initiation factor 2 subunit 1
+Macromolecule #52: Eukaryotic translation initiation factor 2 subunit 3
+Macromolecule #53: Eukaryotic translation initiation factor 1
+Macromolecule #54: Non-structural protein 1
+Macromolecule #18: 18S ribosomal RNA
+Macromolecule #49: tRNA
+Macromolecule #55: ZINC ION
+Macromolecule #56: GUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #57: MAGNESIUM ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |