+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11320 | ||||||||||||
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Title | SARS-CoV-2-Nsp1-40S complex, composite map | ||||||||||||
Map data | |||||||||||||
Sample |
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Function / homology | Function and homology information positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / nucleolus organization / response to extracellular stimulus / positive regulation of endodeoxyribonuclease activity / TNFR1-mediated ceramide production / negative regulation of RNA splicing / neural crest cell differentiation ...positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / nucleolus organization / response to extracellular stimulus / positive regulation of endodeoxyribonuclease activity / TNFR1-mediated ceramide production / negative regulation of RNA splicing / neural crest cell differentiation / rRNA modification in the nucleus and cytosol / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / pigmentation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of ubiquitin protein ligase activity / IRE1-RACK1-PP2A complex / Ribosomal scanning and start codon recognition / positive regulation of Golgi to plasma membrane protein transport / ion channel inhibitor activity / negative regulation of DNA repair / Translation initiation complex formation / oxidized purine DNA binding / negative regulation of Wnt signaling pathway / supercoiled DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / NF-kappaB complex / negative regulation of phagocytosis / ubiquitin-like protein conjugating enzyme binding / fibroblast growth factor binding / regulation of cell division / SARS-CoV-1 modulates host translation machinery / Protein hydroxylation / TOR signaling / iron-sulfur cluster binding / mTORC1-mediated signalling / protein kinase A binding / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Peptide chain elongation / Selenocysteine synthesis / monocyte chemotaxis / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / Formation of a pool of free 40S subunits / positive regulation of cyclic-nucleotide phosphodiesterase activity / phagocytic cup / Eukaryotic Translation Termination / positive regulation of mitochondrial depolarization / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / positive regulation of T cell receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Viral mRNA Translation / positive regulation of activated T cell proliferation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of respiratory burst involved in inflammatory response / L13a-mediated translational silencing of Ceruloplasmin expression / BH3 domain binding / 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) / regulation of translational fidelity / cysteine-type endopeptidase activator activity involved in apoptotic process / ribosomal small subunit export from nucleus / Protein methylation / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / translation regulator activity / Nuclear events stimulated by ALK signaling in cancer / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / stress granule assembly / positive regulation of cell cycle / Mitotic Prometaphase / translation initiation factor binding / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / maturation of SSU-rRNA / EML4 and NUDC in mitotic spindle formation / rough endoplasmic reticulum / gastrulation / laminin binding / spindle assembly / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of apoptotic signaling pathway / signaling adaptor activity / Maturation of protein E / Maturation of protein E / positive regulation of JUN kinase activity / ER Quality Control Compartment (ERQC) / MDM2/MDM4 family protein binding / translational initiation / Myoclonic epilepsy of Lafora / : / FLT3 signaling by CBL mutants Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 / Human (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||
Authors | Schubert K / Karousis ED / Jomaa A / Scaiola A / Echeverria B / Gurzeler L-A / Leibundgut ML / Thiel V / Muehlemann O / Ban N | ||||||||||||
Funding support | Switzerland, 3 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2020 Title: SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. Authors: Katharina Schubert / Evangelos D Karousis / Ahmad Jomaa / Alain Scaiola / Blanca Echeverria / Lukas-Adrian Gurzeler / Marc Leibundgut / Volker Thiel / Oliver Mühlemann / Nenad Ban / Abstract: The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show ...The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome. The protein inserts its C-terminal domain into the mRNA channel, where it interferes with mRNA binding. We observe translation inhibition in the presence of Nsp1 in an in vitro translation system and in human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5' untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines global inhibition of translation by Nsp1 with efficient translation of the viral mRNA to allow expression of viral genes. | ||||||||||||
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_11320.map.gz | 633.4 MB | EMDB map data format | |
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Header (meta data) | emd-11320-v30.xml emd-11320.xml | 49.5 KB 49.5 KB | Display Display | EMDB header |
Images | emd_11320.png | 100.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11320 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11320 | HTTPS FTP |
-Related structure data
Related structure data | 6zojMC 6zokC 6zolC M: atomic model generated by this map C: citing same article (ref.) |
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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_11320.map.gz / Format: CCP4 / Size: 669.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.08 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-Nsp1-40S complex, composite map
+Supramolecule #1: SARS-CoV-2-Nsp1-40S complex, composite map
+Supramolecule #2: Ribosomal proteins
+Supramolecule #3: SARS-CoV-2-Nsp1
+Macromolecule #1: 18S ribosomal RNA
+Macromolecule #2: 40S ribosomal protein SA
+Macromolecule #3: 40S ribosomal protein S3a
+Macromolecule #4: 40S ribosomal protein S2
+Macromolecule #5: 40S ribosomal protein S3
+Macromolecule #6: 40S ribosomal protein S4, X isoform
+Macromolecule #7: 40S ribosomal protein S5
+Macromolecule #8: 40S ribosomal protein S6
+Macromolecule #9: 40S ribosomal protein S7
+Macromolecule #10: 40S ribosomal protein S8
+Macromolecule #11: 40S ribosomal protein S9
+Macromolecule #12: 40S ribosomal protein S10
+Macromolecule #13: 40S ribosomal protein S11
+Macromolecule #14: 40S ribosomal protein S12
+Macromolecule #15: 40S ribosomal protein S13
+Macromolecule #16: 40S ribosomal protein S14
+Macromolecule #17: 40S ribosomal protein S15
+Macromolecule #18: 40S ribosomal protein S16
+Macromolecule #19: 40S ribosomal protein S17
+Macromolecule #20: 40S ribosomal protein S18
+Macromolecule #21: 40S ribosomal protein S19
+Macromolecule #22: 40S ribosomal protein S20
+Macromolecule #23: 40S ribosomal protein S21
+Macromolecule #24: 40S ribosomal protein S15a
+Macromolecule #25: 40S ribosomal protein S23
+Macromolecule #26: 40S ribosomal protein S24
+Macromolecule #27: 40S ribosomal protein S25
+Macromolecule #28: 40S ribosomal protein S26
+Macromolecule #29: 40S ribosomal protein S27
+Macromolecule #30: 40S ribosomal protein S28
+Macromolecule #31: 40S ribosomal protein S29
+Macromolecule #32: 40S ribosomal protein S30
+Macromolecule #33: Ribosomal protein S27a
+Macromolecule #34: Receptor of activated protein C kinase 1
+Macromolecule #35: Non-structural protein 1
+Macromolecule #36: 60S ribosomal protein L41
+Macromolecule #37: MAGNESIUM ION
+Macromolecule #38: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.6 |
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Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K |
-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: 60.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 118765 |