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- EMDB-17804: Bat-Hp-CoV Nsp1 and eIF1 bound to the human 40S small ribosomal s... -
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Open data
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Basic information
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Title | Bat-Hp-CoV Nsp1 and eIF1 bound to the human 40S small ribosomal subunit | ||||||||||||||||||||||||||||||||||||||||||
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![]() | Nsp1 / MERS / SARS / SARS-CoV2 / ribosome / 40S ribosomal subunit / translation inhibition / coronavirus / 43S PIC / 43S pre-initiation complex / mRNA channel / initiation factor / eIF2 / eIF3 / eIF1 / eIF1A / VIRAL PROTEIN / translation | ||||||||||||||||||||||||||||||||||||||||||
Function / homology | ![]() positive regulation of mRNA cis splicing, via spliceosome / : / multi-eIF complex / eukaryotic 43S preinitiation complex / translation factor activity, RNA binding / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / eukaryotic 48S preinitiation complex / response to TNF agonist ...positive regulation of mRNA cis splicing, via spliceosome / : / multi-eIF complex / eukaryotic 43S preinitiation complex / translation factor activity, RNA binding / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / eukaryotic 48S preinitiation complex / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / 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 / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of translational initiation / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / Translation initiation complex formation / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / pigmentation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of cell division / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Peptide chain elongation / organelle membrane / monocyte chemotaxis / Selenocysteine synthesis / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / Formation of a pool of free 40S subunits / phagocytic cup / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / endoplasmic reticulum-Golgi intermediate compartment / ribosomal small subunit binding / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / host cell membrane / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / TOR signaling / T cell proliferation involved in immune response / Major pathway of rRNA processing in the nucleolus and cytosol / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / spindle assembly / regulation of translational fidelity / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / ribosomal small subunit export from nucleus / erythrocyte development / translation regulator activity / Protein methylation / Nuclear events stimulated by ALK signaling in cancer / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / cytosolic ribosome / positive regulation of cell cycle / signaling adaptor activity / negative regulation of smoothened signaling pathway / stress granule assembly / positive regulation of intrinsic apoptotic signaling pathway Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.98 Å | ||||||||||||||||||||||||||||||||||||||||||
![]() | Schubert K / Karousis ED / Ban I / Lapointe CP / Leibundgut M / Baeumlin E / Kummerant E / Scaiola A / Schoenhut T / Ziegelmueller J ...Schubert K / Karousis ED / Ban I / Lapointe CP / Leibundgut M / Baeumlin E / Kummerant E / Scaiola A / Schoenhut T / Ziegelmueller J / Puglisi JD / Muehlemann O / Ban N | ||||||||||||||||||||||||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Universal features of Nsp1-mediated translational shutdown by coronaviruses. Authors: Katharina Schubert / Evangelos D Karousis / Ivo Ban / Christopher P Lapointe / Marc Leibundgut / Emilie Bäumlin / Eric Kummerant / Alain Scaiola / Tanja Schönhut / Jana Ziegelmüller / ...Authors: Katharina Schubert / Evangelos D Karousis / Ivo Ban / Christopher P Lapointe / Marc Leibundgut / Emilie Bäumlin / Eric Kummerant / Alain Scaiola / Tanja Schönhut / Jana Ziegelmüller / Joseph D Puglisi / Oliver Mühlemann / Nenad Ban / ![]() ![]() Abstract: Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ...Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ribosomal mRNA channel to inhibit translation, but it is unclear whether this mechanism is broadly used by coronaviruses, whether the Nsp1 N-terminal domain binds the ribosome, or how Nsp1 allows viral RNAs to be translated. Here, we investigated Nsp1 from SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and Bat-Hp-CoV coronaviruses using structural, biophysical, and biochemical experiments, revealing a conserved role for the C-terminal domain. Additionally, the N-terminal domain of Bat-Hp-CoV Nsp1 binds to the decoding center of the 40S subunit, where it would prevent mRNA and eIF1A accommodation. Structure-based experiments demonstrated the importance of decoding center interactions in all three coronaviruses and showed that the same regions of Nsp1 are necessary for the selective translation of viral RNAs. Our results provide a mechanistic framework to understand how Nsp1 controls preferential translation of viral RNAs. #1: ![]() Title: Universal features of Nsp1-mediated translational shutdown by coronaviruses Authors: Schubert K / Karousis ED / Ban I / Lapointe CP / Leibundgut M / Baeumlin E / Kummerant E / Scaiola A / Schoenhut T / Ziegelmueller J / Puglisi JD / Muehlemann O / Ban N | ||||||||||||||||||||||||||||||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 337.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 63.1 KB 63.1 KB | Display Display | ![]() |
Images | ![]() | 125.8 KB | ||
Masks | ![]() ![]() | 669.9 MB 669.9 MB | ![]() | |
Filedesc metadata | ![]() | 14.6 KB | ||
Others | ![]() ![]() | 620.8 MB 620.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 20.1 KB | Display | |
Data in CIF | ![]() | 24 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ppkMC ![]() 8pplC 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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Voxel size | X=Y=Z: 1.065 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Mask #2
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-Half map: #2
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-Half map: #1
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Sample components
+Entire : Bat-Hp-CoV Nsp1 - eIF1 - 40S complex
+Supramolecule #1: Bat-Hp-CoV Nsp1 - eIF1 - 40S complex
+Macromolecule #1: Eukaryotic translation initiation factor 1
+Macromolecule #3: 40S ribosomal protein SA
+Macromolecule #4: 40S ribosomal protein S3a
+Macromolecule #5: 40S ribosomal protein S2
+Macromolecule #6: 40S ribosomal protein S3
+Macromolecule #7: 40S ribosomal protein S4, X isoform
+Macromolecule #8: 40S ribosomal protein S5
+Macromolecule #9: 40S ribosomal protein S6
+Macromolecule #10: 40S ribosomal protein S7
+Macromolecule #11: 40S ribosomal protein S8
+Macromolecule #12: 40S ribosomal protein S9
+Macromolecule #13: 40S ribosomal protein S10
+Macromolecule #14: 40S ribosomal protein S11
+Macromolecule #15: 40S ribosomal protein S12
+Macromolecule #16: 40S ribosomal protein S13
+Macromolecule #17: 40S ribosomal protein S14
+Macromolecule #18: 40S ribosomal protein S15
+Macromolecule #19: 40S ribosomal protein S16
+Macromolecule #20: 40S ribosomal protein S17
+Macromolecule #21: Small ribosomal subunit protein uS13
+Macromolecule #22: Small ribosomal subunit protein eS19
+Macromolecule #23: 40S ribosomal protein S20
+Macromolecule #24: 40S ribosomal protein S21
+Macromolecule #25: 40S ribosomal protein S15a
+Macromolecule #26: 40S ribosomal protein S23
+Macromolecule #27: 40S ribosomal protein S24
+Macromolecule #28: 40S ribosomal protein S25
+Macromolecule #29: 40S ribosomal protein S26
+Macromolecule #30: 40S ribosomal protein S27
+Macromolecule #31: 40S ribosomal protein S28
+Macromolecule #32: 40S ribosomal protein S29
+Macromolecule #33: Small ribosomal subunit protein eS30
+Macromolecule #34: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #35: Receptor of activated protein C kinase 1
+Macromolecule #36: 60S ribosomal protein L41
+Macromolecule #37: Nsp1
+Macromolecule #2: 18S rRNA
+Macromolecule #38: UNKNOWN ATOM OR ION
+Macromolecule #39: MAGNESIUM ION
+Macromolecule #40: ZINC ION
-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 Component:
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Grid | Model: Quantifoil R2/2 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec. / Details: 15 mA easiGlow Discharge cleaning system (PELCO) | ||||||||
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV | ||||||||
Details | f.c. 80 nM |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 12607 / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.98 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 98750 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Initial model |
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Details | phenix.real_space_refine | |||||||||
Refinement | Space: REAL / Protocol: OTHER | |||||||||
Output model | ![]() PDB-8ppk: |