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- EMDB-49637: SARS-CoV-2 nsp1 bound to the Rhinolophus lepidus 40S ribosome (co... -
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Open data
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Basic information
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Title | SARS-CoV-2 nsp1 bound to the Rhinolophus lepidus 40S ribosome (consensus map) | |||||||||
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![]() | SARS-CoV-2 / RIBOSOME / Seattle Structural Genomics Center for Infectious Disease / SSGCID | |||||||||
Function / homology | ![]() multi-eIF complex / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / eukaryotic 48S preinitiation complex / regulation of translational initiation / ribosomal small subunit binding / translation initiation factor activity / translational initiation / protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism ...multi-eIF complex / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / eukaryotic 48S preinitiation complex / regulation of translational initiation / ribosomal small subunit binding / translation initiation factor activity / translational initiation / protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / Maturation of replicase proteins / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / ISG15-specific peptidase activity / TRAF3-dependent IRF activation pathway / Transcription of SARS-CoV-2 sgRNAs / Translation of Replicase and Assembly of the Replication Transcription Complex / snRNP Assembly / Replication of the SARS-CoV-2 genome / double membrane vesicle viral factory outer membrane / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / host cell endoplasmic reticulum-Golgi intermediate compartment / SARS coronavirus main proteinase / 3'-5'-RNA exonuclease activity / 5'-3' DNA helicase activity / host cell endosome / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / G-quadruplex RNA binding / symbiont-mediated suppression of host toll-like receptor signaling pathway / omega peptidase activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / SARS-CoV-2 modulates host translation machinery / mRNA (guanine-N7)-methyltransferase / host cell Golgi apparatus / methyltransferase cap1 / symbiont-mediated perturbation of host ubiquitin-like protein modification / symbiont-mediated suppression of host NF-kappaB cascade / DNA helicase / methyltransferase cap1 activity / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / forked DNA-dependent helicase activity / single-stranded 3'-5' DNA helicase activity / four-way junction helicase activity / double-stranded DNA helicase activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / regulation of autophagy / host cell perinuclear region of cytoplasm / viral protein processing / lyase activity / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated suppression of host gene expression / copper ion binding / viral translational frameshifting / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / DNA-templated transcription / lipid binding / host cell nucleus / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / nucleus / membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.1 Å | |||||||||
![]() | Gen R / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler D | |||||||||
Funding support | ![]()
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![]() | ![]() Title: SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals. Authors: Risako Gen / Amin Addetia / Daniel Asarnow / Young-Jun Park / Joel Quispe / Matthew C Chan / Jack T Brown / Jimin Lee / Melody G Campbell / Christopher P Lapointe / David Veesler / ![]() Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats-natural reservoirs of sarbecoviruses with a markedly different innate immune system than humans. We reveal that nsp1 potently inhibits translation in Rhinolophus lepidus bat cells, which belong to the same genus as known sarbecovirus reservoir hosts. We determined a cryoelectron microscopy structure of nsp1 bound to the R. lepidus 40S ribosomal subunit, showing that it blocks the mRNA entry channel by targeting a highly conserved site among mammals. Accordingly, we found that nsp1 blocked protein translation in mammalian cells from several species, underscoring its broadly inhibitory activity and conserved role in numerous SARS-CoV-2 hosts. Our findings illuminate the arms race between coronaviruses and mammalian host immunity, providing a foundation for understanding the determinants of viral maintenance in bat hosts and spillover. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 257.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 44.3 KB 44.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 16.7 KB | Display | ![]() |
Images | ![]() | 40.5 KB | ||
Filedesc metadata | ![]() | 10.6 KB | ||
Others | ![]() ![]() ![]() | 483.4 MB 475.7 MB 475.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 878.2 KB | Display | ![]() |
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Full document | ![]() | 877.7 KB | Display | |
Data in XML | ![]() | 26.4 KB | Display | |
Data in CIF | ![]() | 34.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9npz ![]() 9npxC ![]() 9npyC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.829 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_49637_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_49637_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_49637_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
+Entire : SARS-CoV-2 nsp1-Rhinolophus lepidus ribosome complex, consensus map
+Supramolecule #1: SARS-CoV-2 nsp1-Rhinolophus lepidus ribosome complex, consensus map
+Supramolecule #3: SARS-CoV-2 nsp1
+Supramolecule #4: Eukaryotic translation initiation factor 1
+Supramolecule #2: Rhinolophus lepidus 40S ribosomal subunit
+Macromolecule #1: 40S ribosomal protein uS5, RPS2
+Macromolecule #2: 40S ribosomal protein eS4 X isoform, RPS4
+Macromolecule #3: 40S ribosomal protein eS6, RPS6
+Macromolecule #4: 40S ribosomal protein eS8, RPS8
+Macromolecule #5: 40S ribosomal protein uS4, RPS9
+Macromolecule #6: 40S ribosomal protein uS15, RPS13
+Macromolecule #7: 40S ribosomal protein uS11, RPS14
+Macromolecule #8: 40S ribosomal protein uS8, RPS15a
+Macromolecule #9: 40S ribosomal protein eS17, RPS17
+Macromolecule #10: 40S ribosomal protein eS21, RPS21
+Macromolecule #11: 40S ribosomal protein uS12, RPS23
+Macromolecule #12: 40S ribosomal protein eS24, RPS24
+Macromolecule #13: 40S ribosomal protein eS26, RPS26
+Macromolecule #14: 40S ribosomal protein eS27, RPS27
+Macromolecule #15: 40S ribosomal protein eS32, L41
+Macromolecule #16: 40S ribosomal protein uS2, RPSA
+Macromolecule #17: Host translation inhibitor nsp1
+Macromolecule #18: Eukaryotic translation initiation factor 1
+Macromolecule #19: 40S ribosomal protein eS7, RPS7
+Macromolecule #20: 40S ribosomal protein uS17, RPS11
+Macromolecule #21: 40S ribosomal protein eS30, RPS30
+Macromolecule #22: 40S ribosomal protein eS1, RPS3a
+Macromolecule #24: 40S ribosomal protein uS3, RPS3
+Macromolecule #23: 18S ribosomal RNA
+Macromolecule #25: MAGNESIUM ION
+Macromolecule #26: POTASSIUM ION
+Macromolecule #27: ZINC ION
+Macromolecule #28: water
-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: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 30.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |