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Yorodumi- PDB-7tos: E. coli 70S ribosomes bound with the ALS/FTD-associated dipeptide... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7tos | |||||||||||||||
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Title | E. coli 70S ribosomes bound with the ALS/FTD-associated dipeptide repeat protein PR20 | |||||||||||||||
Components |
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Keywords | RIBOSOME / ribosomal binding peptide / ALS/FTD-associated dipeptide repeat protein | |||||||||||||||
Function / homology | Function and homology information DnaA-L2 complex / negative regulation of DNA-templated DNA replication initiation / ribosome assembly / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / ribosomal large subunit assembly / mRNA 5'-UTR binding / large ribosomal subunit / regulation of translation / ribosomal small subunit assembly ...DnaA-L2 complex / negative regulation of DNA-templated DNA replication initiation / ribosome assembly / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / ribosomal large subunit assembly / mRNA 5'-UTR binding / large ribosomal subunit / regulation of translation / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / transferase activity / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / rRNA binding / negative regulation of translation / ribosome / structural constituent of ribosome / translation / ribonucleoprotein complex / response to antibiotic / mRNA binding / RNA binding / zinc ion binding / membrane / metal ion binding / cytoplasm / cytosol Similarity search - Function | |||||||||||||||
Biological species | Escherichia coli (E. coli) Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||
Authors | Loveland, A.B. / Svidritskiy, E. / Susorov, D. / Lee, S. / Park, A. / Zvornicanin, S. / Demo, G. / Gao, F.B. / Korostelev, A.A. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Nat Commun / Year: 2022 Title: Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM. Authors: Anna B Loveland / Egor Svidritskiy / Denis Susorov / Soojin Lee / Alexander Park / Sarah Zvornicanin / Gabriel Demo / Fen-Biao Gao / Andrei A Korostelev / Abstract: Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ...Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two DPR proteins, poly-PR and poly-GR, repress cellular translation but the molecular mechanism remains unknown. Here we show that poly-PR and poly-GR of ≥20 repeats inhibit the ribosome's peptidyl-transferase activity at nanomolar concentrations, comparable to specific translation inhibitors. High-resolution cryogenic electron microscopy (cryo-EM) reveals that poly-PR and poly-GR block the polypeptide tunnel of the ribosome, extending into the peptidyl-transferase center (PTC). Consistent with these findings, the macrolide erythromycin, which binds in the tunnel, competes with poly-PR and restores peptidyl-transferase activity. Our results demonstrate that strong and specific binding of poly-PR and poly-GR in the ribosomal tunnel blocks translation, revealing the structural basis of their toxicity in C9ORF72-ALS/FTD. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7tos.cif.gz | 3.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7tos.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7tos.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/to/7tos ftp://data.pdbj.org/pub/pdb/validation_reports/to/7tos | HTTPS FTP |
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-Related structure data
Related structure data | 26037MC 7tooC 7topC 7toqC 7torC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
+50S ribosomal protein ... , 30 types, 30 molecules L02L03L04L05L06L09L10L11L13L14L15L16L17L18L19L20L22L23L25L27L28L29L30L31L32L33L34L35L36L1
-Ribosomal protein ... , 3 types, 3 molecules L21L24S21
#17: Protein | Mass: 11586.374 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A829CSJ4 |
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#20: Protein | Mass: 11078.874 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A8E0FZY0 |
#51: Protein | Mass: 7763.073 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A8E0HV98 |
-30S ribosomal protein ... , 19 types, 19 molecules S02S03S04S05S06S07S08S09S10S11S12S13S14S15S16S17S18S19S20
#32: Protein | Mass: 25015.816 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: C3TPN2 |
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#33: Protein | Mass: 23078.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A376HTV6 |
#34: Protein | Mass: 23383.002 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: L3PZ69 |
#35: Protein | Mass: 16532.088 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: F4TL26 |
#36: Protein | Mass: 11669.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: P02358 |
#37: Protein | Mass: 16861.523 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: P02359 |
#38: Protein | Mass: 14015.361 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: D8A1L7 |
#39: Protein | Mass: 14554.882 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A1X3KYI7 |
#40: Protein | Mass: 11196.988 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A5B9AU26 |
#41: Protein | Mass: 12388.068 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: I2UH22 |
#42: Protein | Mass: 13636.961 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: I2UHF1 |
#43: Protein | Mass: 12625.753 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A1X3KX08 |
#44: Protein | Mass: 11475.364 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A829E173 |
#45: Protein | Mass: 10159.621 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: D7XN21 |
#46: Protein | Mass: 9207.572 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: B7MIU7 |
#47: Protein | Mass: 9263.946 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A080IK26 |
#48: Protein | Mass: 7606.768 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: E0J6I2 |
#49: Protein | Mass: 9057.626 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: S1EA57 |
#50: Protein | Mass: 9506.190 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: C3TRH7 |
-RNA chain , 3 types, 3 molecules 16S23S5S
#53: RNA chain | Mass: 498725.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 1338015391 |
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#54: RNA chain | Mass: 941305.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 1036415628 |
#55: RNA chain | Mass: 38813.133 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 1370526515 |
-Protein/peptide , 1 types, 1 molecules PR
#56: Protein/peptide | Mass: 5104.186 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) |
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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: E. coli 70S ribosome bound with the ALS/FTD-associated dipeptide repeat protein PR20 Type: RIBOSOME / Entity ID: all / Source: MULTIPLE SOURCES | ||||||||||||
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Molecular weight | Value: 2.5 MDa / Experimental value: NO | ||||||||||||
Source (natural) |
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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: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 35 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
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EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 49219 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 118.39 Å2 | ||||||||||||||||||||||||
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