+Open data
-Basic information
Entry | Database: PDB / ID: 6zvh | ||||||||||||
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Title | EDF1-ribosome complex | ||||||||||||
Components |
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Keywords | RIBOSOME / translation / frameshifting / collision | ||||||||||||
Function / homology | Function and homology information endothelial cell differentiation / 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 / protein tyrosine kinase inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation ...endothelial cell differentiation / 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 / protein tyrosine kinase inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / IRE1-RACK1-PP2A complex / nucleolus organization / : / 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 / laminin receptor activity / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / neural crest cell differentiation / negative regulation of phagocytosis / NF-kappaB complex / rRNA modification in the nucleus and cytosol / transcription regulator inhibitor activity / ubiquitin-like protein conjugating enzyme binding / 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 / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / pigmentation / protein kinase A binding / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / erythrocyte development / Translation initiation complex formation / phagocytic cup / positive regulation of mitochondrial depolarization / negative regulation of Wnt signaling pathway / positive regulation of T cell receptor signaling pathway / positive regulation of transcription by RNA polymerase I / fibroblast growth factor binding / positive regulation of activated T cell proliferation / regulation of cell division / Protein hydroxylation / TOR signaling / iron-sulfur cluster binding / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Selenocysteine synthesis / monocyte chemotaxis / Formation of a pool of free 40S subunits / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of cyclic-nucleotide phosphodiesterase activity / Eukaryotic Translation Termination / ribosomal small subunit export from nucleus / TFIID-class transcription factor complex binding / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / translation regulator activity / Viral mRNA Translation / regulation of lipid metabolic process / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / photoreceptor outer segment / negative regulation of respiratory burst involved in inflammatory response / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / L13a-mediated translational silencing of Ceruloplasmin expression / gastrulation / 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 / regulation of translational fidelity / spindle assembly / MDM2/MDM4 family protein binding / positive regulation of DNA binding / laminin binding / Protein methylation / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Nuclear events stimulated by ALK signaling in cancer / rescue of stalled ribosome / signaling adaptor activity / negative regulation of smoothened signaling pathway / positive regulation of cell cycle / positive regulation of phagocytosis / translation initiation factor binding / stress granule assembly / negative regulation of peptidyl-serine phosphorylation / maturation of SSU-rRNA Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||||||||
Authors | Best, K.M. / Denk, T. / Cheng, J. / Thoms, M. / Berninghausen, O. / Beckmann, R. | ||||||||||||
Funding support | Germany, United States, 3items
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Citation | Journal: Elife / Year: 2020 Title: EDF1 coordinates cellular responses to ribosome collisions. Authors: Niladri K Sinha / Alban Ordureau / Katharina Best / James A Saba / Boris Zinshteyn / Elayanambi Sundaramoorthy / Amit Fulzele / Danielle M Garshott / Timo Denk / Matthias Thoms / Joao A ...Authors: Niladri K Sinha / Alban Ordureau / Katharina Best / James A Saba / Boris Zinshteyn / Elayanambi Sundaramoorthy / Amit Fulzele / Danielle M Garshott / Timo Denk / Matthias Thoms / Joao A Paulo / J Wade Harper / Eric J Bennett / Roland Beckmann / Rachel Green / Abstract: Translation of aberrant mRNAs induces ribosomal collisions, thereby triggering pathways for mRNA and nascent peptide degradation and ribosomal rescue. Here we use sucrose gradient fractionation ...Translation of aberrant mRNAs induces ribosomal collisions, thereby triggering pathways for mRNA and nascent peptide degradation and ribosomal rescue. Here we use sucrose gradient fractionation combined with quantitative proteomics to systematically identify proteins associated with collided ribosomes. This approach identified Endothelial differentiation-related factor 1 (EDF1) as a novel protein recruited to collided ribosomes during translational distress. Cryo-electron microscopic analyses of EDF1 and its yeast homolog Mbf1 revealed a conserved 40S ribosomal subunit binding site at the mRNA entry channel near the collision interface. EDF1 recruits the translational repressors GIGYF2 and EIF4E2 to collided ribosomes to initiate a negative-feedback loop that prevents new ribosomes from translating defective mRNAs. Further, EDF1 regulates an immediate-early transcriptional response to ribosomal collisions. Our results uncover mechanisms through which EDF1 coordinates multiple responses of the ribosome-mediated quality control pathway and provide novel insights into the intersection of ribosome-mediated quality control with global transcriptional regulation. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6zvh.cif.gz | 1.8 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6zvh.ent.gz | 1.3 MB | Display | PDB format |
PDBx/mmJSON format | 6zvh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zv/6zvh ftp://data.pdbj.org/pub/pdb/validation_reports/zv/6zvh | HTTPS FTP |
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-Related structure data
Related structure data | 11456MC 6zviC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 2 types, 2 molecules 2x
#1: RNA chain | Mass: 561308.438 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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#35: RNA chain | Mass: 24004.262 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
+40S ribosomal protein ... , 31 types, 31 molecules ABDEFHIKLPQRSTUVXacdCGJMNOWYZbe
-Protein , 4 types, 4 molecules gfyi
#22: Protein | Mass: 34669.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
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#34: Protein | Mass: 7884.286 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
#36: Protein | Mass: 8557.207 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9NX58 |
#37: Protein | Mass: 12330.996 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O60869 |
-Non-polymers , 2 types, 33 molecules
#38: Chemical | ChemComp-MG / #39: 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 |
-Sample preparation
Component | Name: EDF1-ribosome complex / Type: RIBOSOME / Entity ID: #1-#37 / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 28 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 81976 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 55.5 Å2 | ||||||||||||||||||||||||
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