+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22432 | |||||||||
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Title | SARS-CoV-2 Nsp1 and rabbit 40S ribosome complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | cryo-EM / single particle / protein expression inhibition / RIBOSOME-VIRAL PROTEIN complex | |||||||||
Function / homology | Function and homology information negative regulation of RNA splicing / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / laminin receptor activity / Ribosomal scanning and start codon recognition / Translation initiation complex formation / mammalian oogenesis stage / activation-induced cell death of T cells / fibroblast growth factor binding ...negative regulation of RNA splicing / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / laminin receptor activity / Ribosomal scanning and start codon recognition / Translation initiation complex formation / mammalian oogenesis stage / activation-induced cell death of T cells / fibroblast growth factor binding / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / phagocytic cup / ubiquitin ligase inhibitor activity / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / L13a-mediated translational silencing of Ceruloplasmin expression / 90S preribosome / T cell proliferation involved in immune response / Major pathway of rRNA processing in the nucleolus and cytosol / erythrocyte development / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Protein methylation / translation regulator activity / ribosomal small subunit export from nucleus / cytosolic ribosome / laminin binding / 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) / rough endoplasmic reticulum / Maturation of protein E / Maturation of protein E / gastrulation / ER Quality Control Compartment (ERQC) / MDM2/MDM4 family protein binding / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / NOTCH3 Activation and Transmission of Signal to the Nucleus / APC-Cdc20 mediated degradation of Nek2A / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / PINK1-PRKN Mediated Mitophagy / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Regulation of pyruvate metabolism / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / Downregulation of ERBB2:ERBB3 signaling / DNA-(apurinic or apyrimidinic site) lyase / NF-kB is activated and signals survival / Regulation of PTEN localization / NRIF signals cell death from the nucleus / Regulation of BACH1 activity / rescue of stalled ribosome / Activated NOTCH1 Transmits Signal to the Nucleus / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLK / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / EGFR downregulation / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Oryctolagus cuniculus (rabbit) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
Authors | Yuan S / Xiong Y | |||||||||
Citation | Journal: Mol Cell / Year: 2020 Title: Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA. Authors: Shuai Yuan / Lei Peng / Jonathan J Park / Yingxia Hu / Swapnil C Devarkar / Matthew B Dong / Qi Shen / Shenping Wu / Sidi Chen / Ivan B Lomakin / Yong Xiong / Abstract: The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here ...The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Differential expression analysis of mRNA-seq data revealed that Nsp1 broadly alters the cellular transcriptome. Our cryo-EM structure of the Nsp1-40S ribosome complex shows that Nsp1 inhibits translation by plugging the mRNA entry channel of the 40S. We also determined the structure of the 48S preinitiation complex formed by Nsp1, 40S, and the cricket paralysis virus internal ribosome entry site (IRES) RNA, which shows that it is nonfunctional because of the incorrect position of the mRNA 3' region. Our results elucidate the mechanism of host translation inhibition by SARS-CoV-2 and advance understanding of the impacts from a major pathogenicity factor of 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_22432.map.gz | 118.1 MB | EMDB map data format | |
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Header (meta data) | emd-22432-v30.xml emd-22432.xml | 48.8 KB 48.8 KB | Display Display | EMDB header |
Images | emd_22432.png | 141.4 KB | ||
Filedesc metadata | emd-22432.cif.gz | 11.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22432 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22432 | HTTPS FTP |
-Validation report
Summary document | emd_22432_validation.pdf.gz | 528.7 KB | Display | EMDB validaton report |
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Full document | emd_22432_full_validation.pdf.gz | 528.2 KB | Display | |
Data in XML | emd_22432_validation.xml.gz | 6.7 KB | Display | |
Data in CIF | emd_22432_validation.cif.gz | 7.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22432 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22432 | HTTPS FTP |
-Related structure data
Related structure data | 7jqbMC 7jqcC 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_22432.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.068 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 and rabbit 40S ribosome complex
+Supramolecule #1: SARS-CoV-2 Nsp1 and rabbit 40S ribosome complex
+Supramolecule #2: SARS-CoV-2 Nsp1
+Supramolecule #3: rabbit 40S ribosome
+Macromolecule #1: rRNA
+Macromolecule #2: eS25
+Macromolecule #3: 40S ribosomal protein SA
+Macromolecule #4: 40S ribosomal protein S26
+Macromolecule #5: eS1
+Macromolecule #6: uS5
+Macromolecule #7: eS28
+Macromolecule #8: Ribosomal protein S3
+Macromolecule #9: eS30
+Macromolecule #10: uS7
+Macromolecule #11: eS31
+Macromolecule #12: eS6
+Macromolecule #13: RACK1
+Macromolecule #14: eS7
+Macromolecule #15: eS8
+Macromolecule #16: uS4
+Macromolecule #17: S10_plectin domain-containing protein
+Macromolecule #18: eS12
+Macromolecule #19: uS19
+Macromolecule #20: Uncharacterized protein
+Macromolecule #21: eS17
+Macromolecule #22: uS13
+Macromolecule #23: Uncharacterized protein
+Macromolecule #24: uS10
+Macromolecule #25: 40S ribosomal protein S21
+Macromolecule #26: 40S ribosomal protein S24
+Macromolecule #27: Host translation inhibitor nsp1
+Macromolecule #28: 40S ribosomal protein S4
+Macromolecule #29: uS17
+Macromolecule #30: uS15
+Macromolecule #31: Uncharacterized protein
+Macromolecule #32: uS8
+Macromolecule #33: Uncharacterized protein
+Macromolecule #34: eS27
-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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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 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 |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 353927 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |