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Open data
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Basic information
| Entry | Database: PDB / ID: 9cn3 | ||||||||||||||||||||||||
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| Title | Human 39S mitoribosome in complex with antibiotic Linezolid | ||||||||||||||||||||||||
Components |
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Keywords | RIBOSOME/ANTIBIOTIC / Mitochondrial ribosome / Oxazolidinone / antibiotics / RIBOSOME-ANTIBIOTIC complex | ||||||||||||||||||||||||
| Function / homology | Function and homology informationmitochondrial translational termination / mitochondrial transcription / mitochondrial translational elongation / Mitochondrial translation elongation / Mitochondrial translation termination / translation release factor activity, codon nonspecific / Mitochondrial translation initiation / translation release factor activity / mitochondrial large ribosomal subunit / peptidyl-tRNA hydrolase ...mitochondrial translational termination / mitochondrial transcription / mitochondrial translational elongation / Mitochondrial translation elongation / Mitochondrial translation termination / translation release factor activity, codon nonspecific / Mitochondrial translation initiation / translation release factor activity / mitochondrial large ribosomal subunit / peptidyl-tRNA hydrolase / mitochondrial ribosome / mitochondrial small ribosomal subunit / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / peptidyl-tRNA hydrolase activity / mitochondrial translation / anatomical structure morphogenesis / RNA processing / Mitochondrial protein degradation / rescue of stalled ribosome / cellular response to leukemia inhibitory factor / fibrillar center / cell junction / double-stranded RNA binding / large ribosomal subunit / small ribosomal subunit rRNA binding / large ribosomal subunit rRNA binding / endonuclease activity / mitochondrial inner membrane / negative regulation of translation / rRNA binding / nuclear body / structural constituent of ribosome / ribosome / translation / mitochondrial matrix / ribonucleoprotein complex / protein domain specific binding / nucleotide binding / mRNA binding / apoptotic process / positive regulation of DNA-templated transcription / nucleolus / mitochondrion / RNA binding / nucleoplasm / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.62 Å | ||||||||||||||||||||||||
Authors | Raskar, T. / Bibel, B. / Galonic Fujimori, D. / Fraser, J. | ||||||||||||||||||||||||
| Funding support | United States, 1items
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Citation | Journal: Nucleic Acids Res / Year: 2025Title: Context-specific inhibition of mitochondrial ribosomes by phenicol and oxazolidinone antibiotics. Authors: Brianna Bibel / Tushar Raskar / Mary Couvillion / Muhoon Lee / Jordan I Kleinman / Nono Takeuchi-Tomita / L Stirling Churchman / James S Fraser / Danica Galonić Fujimori / ![]() Abstract: The antibiotics chloramphenicol (CHL) and oxazolidinones, including linezolid (LZD), are known to inhibit mitochondrial translation. This can result in serious, potentially deadly, side effects when ...The antibiotics chloramphenicol (CHL) and oxazolidinones, including linezolid (LZD), are known to inhibit mitochondrial translation. This can result in serious, potentially deadly, side effects when used therapeutically. Although the mechanism by which CHL and LZD inhibit bacterial ribosomes has been elucidated in detail, their mechanism of action against mitochondrial ribosomes has yet to be explored. CHL and oxazolidinones bind to the ribosomal peptidyl transfer center (PTC) of the bacterial ribosome and prevent incorporation of incoming amino acids under specific sequence contexts, causing ribosomes to stall only at certain sequences. Through mitoribosome profiling, we show that inhibition of mitochondrial ribosomes is similarly context-specific-CHL and LZD lead to mitoribosome stalling primarily when there is an alanine, serine, or threonine in the penultimate position of the nascent peptide chain. We further validate context-specific stalling through in vitro translation assays. A high-resolution cryo-electron microscopy structure of LZD bound to the PTC of the human mitoribosome shows extensive similarity to the mode of bacterial inhibition and also suggests potential avenues for altering selectivity. Our findings could help inform the rational development of future, less mitotoxic, antibiotics, which are critically needed in the current era of increasing antimicrobial resistance. | ||||||||||||||||||||||||
| History |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9cn3.cif.gz | 2.7 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb9cn3.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9cn3.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9cn3_validation.pdf.gz | 1.9 MB | Display | wwPDB validaton report |
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| Full document | 9cn3_full_validation.pdf.gz | 2.1 MB | Display | |
| Data in XML | 9cn3_validation.xml.gz | 268.5 KB | Display | |
| Data in CIF | 9cn3_validation.cif.gz | 457.6 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cn/9cn3 ftp://data.pdbj.org/pub/pdb/validation_reports/cn/9cn3 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 45757MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
+39S ribosomal protein ... , 46 types, 48 molecules 0123456789DEFHIJKLMNOQRSTUVWXY...
-RNA chain , 2 types, 2 molecules AB
| #11: RNA chain | Mass: 500019.594 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 1563835895 |
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| #12: RNA chain | Mass: 22961.699 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 1896813692 |
-Protein , 6 types, 6 molecules Pjopqu
| #24: Protein | Mass: 20465.348 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A8K9D2 |
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| #44: Protein | Mass: 13696.684 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A8K7J6 |
| #48: Protein | Mass: 12292.333 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9BQC6 |
| #49: Protein | Mass: 23674.203 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q14197, peptidyl-tRNA hydrolase |
| #50: Protein | Mass: 25426.895 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q8TAE8 |
| #53: Protein | Mass: 60442.441 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
-Non-polymers , 4 types, 4235 molecules 






| #55: Chemical | | #56: Chemical | ChemComp-MG / #57: Chemical | ChemComp-ZLD / | #58: Water | ChemComp-HOH / | |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | N |
-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: 39S subunit of human mitochondrial ribosome in complex with Linezolid Type: RIBOSOME / Details: Purified from freestyle 293 cells / Entity ID: #1-#54 / Source: NATURAL |
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| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.4 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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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: 2000 nm / Nominal defocus min: 500 nm |
| Image recording | Electron dose: 21 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
| Software | Name: PHENIX / Version: 1.20.1_4487: phenix.real_space_refine / Classification: refinement |
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
| 3D reconstruction | Resolution: 2.62 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 347872 / Symmetry type: POINT |
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About Yorodumi




Homo sapiens (human)
United States, 1items
Citation

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FIELD EMISSION GUN