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Yorodumi- PDB-7nsq: Structure of ErmDL-Telithromycin-stalled 70S E. coli ribosomal co... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7nsq | |||||||||
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Title | Structure of ErmDL-Telithromycin-stalled 70S E. coli ribosomal complex with A and P-tRNA | |||||||||
Components |
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Keywords | RIBOSOME / Antibiotic / ErmDL / Telithromycin / Macrolide / Stalling | |||||||||
Function / homology | Function and homology information transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / ribosome assembly / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly ...transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / ribosome assembly / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / DNA-templated transcription termination / response to radiation / ribosomal large subunit assembly / mRNA 5'-UTR binding / large ribosomal subunit / 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 / tRNA binding / cytoplasmic translation / rRNA binding / negative regulation of translation / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / response to antibiotic / negative regulation of DNA-templated transcription / mRNA binding / DNA binding / RNA binding / zinc ion binding / membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Escherichia coli (E. coli) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Beckert, B. / Wilson, D.N. | |||||||||
Funding support | Germany, 2items
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Citation | Journal: Nat Commun / Year: 2021 Title: Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics. Authors: Bertrand Beckert / Elodie C Leroy / Shanmugapriya Sothiselvam / Lars V Bock / Maxim S Svetlov / Michael Graf / Stefan Arenz / Maha Abdelshahid / Britta Seip / Helmut Grubmüller / Alexander ...Authors: Bertrand Beckert / Elodie C Leroy / Shanmugapriya Sothiselvam / Lars V Bock / Maxim S Svetlov / Michael Graf / Stefan Arenz / Maha Abdelshahid / Britta Seip / Helmut Grubmüller / Alexander S Mankin / C Axel Innis / Nora Vázquez-Laslop / Daniel N Wilson / Abstract: Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are ...Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are known to interrupt translation at specific sequence motifs, with ketolides predominantly stalling at Arg/Lys-X-Arg/Lys motifs and macrolides displaying a broader specificity, a structural basis for their context-specific action has been lacking. Here, we present structures of ribosomes arrested during the synthesis of an Arg-Leu-Arg sequence by the macrolide erythromycin (ERY) and the ketolide telithromycin (TEL). Together with deep mutagenesis and molecular dynamics simulations, the structures reveal how ERY and TEL interplay with the Arg-Leu-Arg motif to induce translational arrest and illuminate the basis for the less stringent sequence-specific action of ERY over TEL. Because programmed stalling at the Arg/Lys-X-Arg/Lys motifs is used to activate expression of antibiotic resistance genes, our study also provides important insights for future development of improved macrolide antibiotics. | |||||||||
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 | 7nsq.cif.gz | 3.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7nsq.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7nsq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7nsq_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 7nsq_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 7nsq_validation.xml.gz | 216.2 KB | Display | |
Data in CIF | 7nsq_validation.cif.gz | 374.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ns/7nsq ftp://data.pdbj.org/pub/pdb/validation_reports/ns/7nsq | HTTPS FTP |
-Related structure data
Related structure data | 12575MC 7nsoC 7nspC 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 , 6 types, 6 molecules AB68av
#1: RNA chain | Mass: 941306.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 170787319 |
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#2: RNA chain | Mass: 38790.090 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: CP035706.1 |
#32: RNA chain | Mass: 1829.109 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) |
#34: RNA chain | Mass: 28094.645 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 1430654817 |
#35: RNA chain | Mass: 499054.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 1476653947 |
#56: RNA chain | Mass: 24796.779 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 1848841577 |
+50S ribosomal protein ... , 29 types, 29 molecules CDEFGHJKLMNOPQRSTUVWXYZ012345
-30S ribosomal protein ... , 20 types, 20 molecules bcdefghijklmnopqrstu
#36: Protein | Mass: 24971.764 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A3K3SDJ5 |
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#37: Protein | Mass: 23078.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A773VR79 |
#38: Protein | Mass: 23383.002 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: V0YKB3 |
#39: Protein | Mass: 16532.088 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: T9SGC3 |
#40: Protein | Mass: 11582.294 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: W8T6F0 |
#41: 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 |
#42: Protein | Mass: 14015.361 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: H4JDM0 |
#43: Protein | Mass: 14554.882 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A6L7FQ03 |
#44: 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 |
#45: Protein | Mass: 12487.200 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A5I5F5V9 |
#46: 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 |
#47: Protein | Mass: 12625.753 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: I2X719 |
#48: Protein | Mass: 11475.364 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A1X3K3H0 |
#49: Protein | Mass: 10159.621 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: E9YUR8 |
#50: Protein | Mass: 9207.572 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: C3SYP2 |
#51: Protein | Mass: 9263.946 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: T6LV72 |
#52: Protein | Mass: 7734.896 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: I2SQR9 |
#53: Protein | Mass: 9421.018 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: A0A7G6HV07 |
#54: Protein | Mass: 9577.268 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: I4T5W9 |
#55: Protein | Mass: 8392.844 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: UniProt: E9TH65 |
-Protein/peptide / Non-polymers , 2 types, 2 molecules 7
#33: Protein/peptide | Mass: 877.087 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) |
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#57: Chemical | ChemComp-TEL / |
-Details
Has ligand of interest | Y |
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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: Structure of ErmDL-Erythromycin-stalled 70S E. coli ribosomal complex with P-tRNA Type: RIBOSOME / Entity ID: #1-#56 / Source: NATURAL |
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Molecular weight | Experimental value: YES |
Source (natural) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: Quantifoil R3/3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % |
-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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 35 sec. / Electron dose: 1 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 433827 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 83696 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL |