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- PDB-8ppk: 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
Entry | Database: PDB / ID: 8ppk | ||||||||||||||||||||||||||||||||||||||||||
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Title | Bat-Hp-CoV Nsp1 and eIF1 bound to the human 40S small ribosomal subunit | ||||||||||||||||||||||||||||||||||||||||||
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![]() | TRANSLATION / 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 | ||||||||||||||||||||||||||||||||||||||||||
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 / response to TNF agonist / positive regulation of base-excision repair ...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 / response to TNF agonist / positive regulation of base-excision repair / eukaryotic 48S preinitiation complex / 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 DNA repair / negative regulation of RNA splicing / 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 / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / pigmentation / organelle membrane / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / 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 / monocyte chemotaxis / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / cysteine-type endopeptidase activator activity involved in apoptotic process / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / phagocytic cup / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / Response of EIF2AK4 (GCN2) to amino acid deficiency / endoplasmic reticulum-Golgi intermediate compartment / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response / ribosomal small subunit binding / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / host cell membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / 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 / TOR signaling / T cell proliferation involved in immune response / spindle assembly / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / erythrocyte development / Protein methylation / negative regulation of ubiquitin-dependent protein catabolic process / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / translation regulator activity / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Nuclear events stimulated by ALK signaling in cancer / ribosomal small subunit export from nucleus / positive regulation of cell cycle / signaling adaptor activity / cytosolic ribosome / negative regulation of smoothened signaling pathway / positive regulation of intrinsic apoptotic signaling pathway Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.98 Å | ||||||||||||||||||||||||||||||||||||||||||
![]() | Schubert, K. / Karousis, E.D. / Ban, I. / Lapointe, C.P. / Leibundgut, M. / Baeumlin, E. / Kummerant, E. / Scaiola, A. / Schoenhut, T. / Ziegelmueller, J. ...Schubert, K. / Karousis, E.D. / Ban, I. / Lapointe, C.P. / Leibundgut, M. / Baeumlin, E. / Kummerant, E. / Scaiola, A. / Schoenhut, T. / Ziegelmueller, J. / Puglisi, J.D. / 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, E.D. / Ban, I. / Lapointe, C.P. / Leibundgut, M. / Baeumlin, E. / Kummerant, E. / Scaiola, A. / Schoenhut, T. / Ziegelmueller, J. / Puglisi, J.D. / Muehlemann, O. / Ban, N. | ||||||||||||||||||||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 2 MB | Display | ![]() |
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PDB format | ![]() | 1.6 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 17804MC ![]() 8pplC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 4 types, 4 molecules pfgj
#1: Protein | Mass: 12752.498 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#34: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: 1-76: ubiquitin zinc finger protein / Source: (natural) ![]() |
#35: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#37: Protein | Mass: 21172.863 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: residues 1-174 of Bat-Hp-betacoronavirus/Zhejiang2013 polyprotein ORF1ab Source: (gene. exp.) ![]() ![]() ![]() |
+40S ribosomal protein ... , 28 types, 28 molecules ABCDEFGHIJKLMNOPQRUVWXYZabcd
-Small ribosomal subunit protein ... , 3 types, 3 molecules STe
#21: Protein | Mass: 17801.814 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: S2: acetylserine (SAC) / Source: (natural) ![]() |
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#22: Protein | Mass: 16104.579 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: R67: omega-methylarginine (NMM) / Source: (natural) ![]() |
#33: Protein | Mass: 14415.724 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: 1-74: ubiquitin / Source: (natural) ![]() |
-RNA chain / Protein/peptide , 2 types, 2 molecules 2h
#2: RNA chain | Mass: 603609.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: unmodified rRNA sequence: >18S_rRNA_taoka_unmodified UACCUGGUUGAUCCUGCCAGUAGCAUaUGCUUGuCuCAAAGAUUAAGCCAUGCAUGUCUA AGUACGCACGGCCGGUACAGUGAAACUGCGAAuGGCUCaUUAAAuCAGuUAUGGUuCCuU ...Details: unmodified rRNA sequence: >18S_rRNA_taoka_unmodified UACCUGGUUGAUCCUGCCAGUAGCAUaUGCUUGuCuCAAAGAUUAAGCCAUGCAUGUCUA AGUACGCACGGCCGGUACAGUGAAACUGCGAAuGGCUCaUUAAAuCAGuUAUGGUuCCuU uGGUCGCUCGCUCCUCUCCUACUUGGAUAACUGUGGUAaUUCUAGaGCUAAuAcAUGCCG ACGGGCGCUGACCCCCUUCGCGGGGGGGAuGCGUGCAuUUAUCAGAUCAAAACCAACCCG GUCAGCCCCUCUCCGGCCCCGGCCGGGGGGCGGGCGCCGGCGGCUUUGGUGACUCuAGAU AACCUCGGGCCGAUCGCACGCCCCCCGUGGCGGCGACGACCCAUUCGAACGUCuGCCCUA UCAACUUUCGAUGGUAGUCGCCGUGCCUACCAUGGUGACCACGGGuGACGGGGAAUCAGG GUUCGAUuCCGGAGAgGGAGCCUGAGAAACGGCUACCACAUcCAAGGaAGGCAGCAGGCG CGCaAAUUACCCACUCCCGACCCGGGGAgGUaGUGAcGAAAAAUAACAAUACAGGACUCU UUCGAGGCCCUGUAAUUGGAAUGAGUCCACUuUAAaUCCUUUAACGAGGaUCCAUUGGAG gGCAAGUCuGGUGCCAGCAGcCGCGGuAAUUCCAGCUCCAAUAgCGUAuAuUAAAGUUGC UGCAGUUaAAAAGCUCGUAGuUgGAuCUUGGGAGCGGGCGGGCGGUCCGCCGCGAGGCGA GCCACCGCCCGUCCCCGCCCCUUGCCUCUCGGCGCCCCCUCGAUGCUCUUAGCUGAGUGU CCCGCGGGGCCCGAAGcGuUuACUUUGAAAAAAuuAGAGUGuUCAAAGCAGGCCCGAGCC GCCUGGAUACCGCAGCUAGGAAuAAugGAAUAGGACCGCGGUUCUAUUUUGUUGGUuUUC GGAACUGAGGCCAUGAUuAAGAGGGACGGCCGGGGGCAUUCGUAUUGCGCCGCUAGAGGU GAAAUuCUUGGACCGGCGCAAGACGGACCAGAGCGAAAGCAUUuGCCAAGAAUGUUUUCA UUAAUCAAGAaCGAAAGUCGGAGGuuCGAAGACGAuCAGAUACCGUCGUAGUUCCGACCA uAAACGAUGCCGACCGGCGAUGCGGCGGCGUUAUUCCCAUGACCCGCCGGGCAGCuUCCG GGAAACCAAAGUCUUUGGGUUCCGGGGGGAGUAuGGuUGCAAAGCUGAAACUUAAAGGAA UUGACGGAAGGGCACCACCAGGAGUGGAGCCuGCGGCuUAAUUuGACuCAACACGGGAAA CCUCACCCGGCcCGGACACGGACAGGAuUGACAGAUUGAUAGCUCUUUCUCGAUUCCGUG GGUGGuGgUGCAUGGCcGUUCUUAGUuGGUGGAGCGAUUUGUCUGGuUAAUUCCGAUAAC GAaCGAGACUcUGGCAUGCUAACUAGUUACGCGACCCCCGAGCGGUCGGCGUCCCCCAAC UuCUuAgAGGGACAAGUGGCGUUCAGCCACCCGAGAUUGAGCAAUAACAgGUCUGUGAUG CCCUUAGAUGUCCGGGGCUGCACGCGCGCUACACUGACUGGCUCAGCGUGUGCCUACCCU ACGCCGGCAGGCGCGGGUAACCCGUUGAACCCCAUUCGUGAUGGGGAUCGGGGAUUGCAA UUAUuCCCCAUGAACGAGgAAUuCCCAGUAAGUGCGGGUCAUAAGCUuGCGUUGAUUaAG UCCCUGCCCUUuGUACACACCGcCCGUCGCUACUACCGAUUGGAUGGUUUAGUGAGGCCC UCGGAUCGGCCCCGCCGGGGUCGGCCCACGGCCCUGGCGGAGCGCUGAGAAGACGGUCGA ACUuGACUAUCUAGAGGAAGUAAAAGUCGUAaCAAGGUUUCcGUAGGUGaaCCUGCGGAA GGAUCAUUA Source: (natural) ![]() |
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#36: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: large subunit protein associated with small subunit Source: (natural) ![]() |
-Non-polymers , 3 types, 231 molecules ![](data/chem/img/UNX.gif)
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#38: Chemical | ChemComp-UNX / #39: Chemical | ChemComp-MG / #40: Chemical | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Bat-Hp-CoV Nsp1 - eIF1 - 40S complex / Type: RIBOSOME / Entity ID: #1-#37 / Source: NATURAL | ||||||||||||||||
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Molecular weight | Units: MEGADALTONS / Experimental value: NO | ||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: f.c. 80 nM | ||||||||||||||||
Specimen support | Details: 15 mA easiGlow Discharge cleaning system (PELCO) / Grid material: COPPER / Grid type: Quantifoil R2/2 | ||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 81000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 600 nm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 12607 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.98 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 98750 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL / Details: phenix.real_space_refine | ||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
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Refine LS restraints |
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