+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22433 | |||||||||
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Title | SARS-CoV-2 Nsp1, CrPV IRES 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 ribosomal subunit / negative regulation of RNA splicing / rRNA modification in the nucleus and cytosol / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / Translation initiation complex formation / fibroblast growth factor binding / SARS-CoV-1 modulates host translation machinery / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) ...ribosomal subunit / negative regulation of RNA splicing / rRNA modification in the nucleus and cytosol / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / Translation initiation complex formation / fibroblast growth factor binding / SARS-CoV-1 modulates host translation machinery / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / 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 / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / 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 / Protein methylation / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / 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 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Constitutive Signaling by NOTCH1 HD Domain Mutants / Endosomal Sorting Complex Required For Transport (ESCRT) / NOTCH2 Activation and Transmission of Signal to the Nucleus / 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 / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Downregulation of ERBB4 signaling / p75NTR recruits signalling complexes / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / InlA-mediated entry of Listeria monocytogenes into host cells / Pexophagy / Regulation of innate immune responses to cytosolic DNA / VLDLR internalisation and degradation / DNA-(apurinic or apyrimidinic site) lyase / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Activated NOTCH1 Transmits Signal to the Nucleus / Translesion synthesis by REV1 / NF-kB is activated and signals survival / Regulation of PTEN localization / Translesion synthesis by POLK / Regulation of BACH1 activity / small-subunit processome / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / cytosolic ribosome / Downregulation of TGF-beta receptor signaling / Josephin domain DUBs / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / 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 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / TNFR1-induced NF-kappa-B signaling pathway / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / SCF-beta-TrCP mediated degradation of Emi1 / Regulation of NF-kappa B signaling / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / Negative regulators of DDX58/IFIH1 signaling / TNFR2 non-canonical NF-kB pathway / NOTCH3 Activation and Transmission of Signal to the Nucleus / activated TAK1 mediates p38 MAPK activation / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Deactivation of the beta-catenin transactivating complex / Degradation of DVL Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Cricket paralysis virus / Oryctolagus cuniculus (rabbit) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 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_22433.map.gz | 59.8 MB | EMDB map data format | |
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Header (meta data) | emd-22433-v30.xml emd-22433.xml | 50.4 KB 50.4 KB | Display Display | EMDB header |
Images | emd_22433.png | 130.6 KB | ||
Filedesc metadata | emd-22433.cif.gz | 11.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22433 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22433 | HTTPS FTP |
-Related structure data
Related structure data | 7jqcMC 7jqbC 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_22433.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, CrPV IRES, and rabbit 40S ribosome complex
+Supramolecule #1: SARS-CoV-2 Nsp1, CrPV IRES, and rabbit 40S ribosome complex
+Supramolecule #2: SARS-CoV-2 Nsp1
+Supramolecule #3: CrPV IRES
+Supramolecule #4: rabbit 40S ribosome
+Macromolecule #1: rRNA
+Macromolecule #28: Cricket paralysis virus IRES RNA
+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 #29: 40S ribosomal protein S4
+Macromolecule #30: uS17
+Macromolecule #31: uS15
+Macromolecule #32: Uncharacterized protein
+Macromolecule #33: uS8
+Macromolecule #34: Uncharacterized protein
+Macromolecule #35: 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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 48689 |