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Open data
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Basic information
| Entry | Database: PDB / ID: 8k2b | ||||||
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| Title | Cryo-EM structure of the human 39S mitoribosome with Tigecycline | ||||||
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Keywords | RIBOSOME / 39S mitoribosome / Tigecycline / antibiotic | ||||||
| Function / homology | Function and homology informationnegative regulation of mitochondrial translation / negative regulation of ribosome biogenesis / Mitochondrial Fatty Acid Beta-Oxidation / Protein lipoylation / positive regulation of mitochondrial translation / mitochondrial large ribosomal subunit assembly / Complex I biogenesis / Respiratory electron transport / mitochondrial translational termination / mitochondrial translational elongation ...negative regulation of mitochondrial translation / negative regulation of ribosome biogenesis / Mitochondrial Fatty Acid Beta-Oxidation / Protein lipoylation / positive regulation of mitochondrial translation / mitochondrial large ribosomal subunit assembly / Complex I biogenesis / Respiratory electron transport / mitochondrial translational termination / mitochondrial translational elongation / translation release factor activity, codon nonspecific / Mitochondrial translation elongation / Mitochondrial translation initiation / Mitochondrial ribosome-associated quality control / protein lipoylation / mitochondrial fission / iron-sulfur cluster assembly complex / Mitochondrial translation termination / peptidyl-tRNA hydrolase / mitochondrial large ribosomal subunit / mitochondrial large ribosomal subunit binding / mitochondrial [2Fe-2S] assembly complex / mitochondrial ribosome / mitochondrial small ribosomal subunit / peptidyl-tRNA hydrolase activity / mitochondrial translation / [2Fe-2S] cluster assembly / iron-sulfur cluster assembly / ribosomal large subunit binding / proton motive force-driven mitochondrial ATP synthesis / mitochondrial electron transport, NADH to ubiquinone / acyl binding / mitochondrial respiratory chain complex I assembly / respiratory chain complex I / anatomical structure morphogenesis / acyl carrier activity / RNA processing / Mitochondrial protein degradation / rescue of stalled cytosolic ribosome / aerobic respiration / fatty acid binding / cellular response to leukemia inhibitory factor / ribosomal large subunit biogenesis / mitochondrial membrane / fibrillar center / fatty acid biosynthetic process / cell junction / double-stranded RNA binding / large ribosomal subunit / small ribosomal subunit rRNA binding / endonuclease activity / large ribosomal subunit rRNA binding / 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 / hydrolase activity / mRNA binding / apoptotic process / calcium ion binding / nucleolus / structural molecule activity / 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: 3.4 Å | ||||||
Authors | Li, X. / Wang, M. / Cheng, J. | ||||||
| Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2024Title: Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline. Authors: Xiang Li / Mengjiao Wang / Timo Denk / Robert Buschauer / Yi Li / Roland Beckmann / Jingdong Cheng / ![]() Abstract: Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, ...Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy. | ||||||
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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 | 8k2b.cif.gz | 2.3 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8k2b.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8k2b.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k2/8k2b ftp://data.pdbj.org/pub/pdb/validation_reports/k2/8k2b | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 36837MC ![]() 8k2aC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yooC ![]() 8yopC 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
-RNA chain , 2 types, 2 molecules L1L2
| #1: RNA chain | Mass: 500019.594 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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| #2: RNA chain | Mass: 22022.131 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
+Large ribosomal subunit protein ... , 47 types, 47 molecules LBLCLDLILJLKLMLNLOLPLQLSLTLULWLXLaLbLuLdLfLgLhLiLjLkLlLmLnLo...
-Mitochondrial ... , 3 types, 3 molecules LRuv
| #14: 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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| #53: Protein | Mass: 26203.076 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q96EH3 |
| #54: Protein | Mass: 8460.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: L0R8F8 |
-39S ribosomal protein ... , 2 types, 2 molecules LVLz
| #18: Protein | Mass: 24369.527 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: E7ESL0 |
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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 |
-Protein , 1 types, 1 molecules w
| #55: Protein | Mass: 17434.273 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O14561 |
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-Non-polymers , 4 types, 100 molecules 






| #56: Chemical | ChemComp-MG / #57: Chemical | ChemComp-T1C / | #58: Chemical | #59: Chemical | ChemComp-PNS / | |
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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: 55S mitoribosome with tigecycline / Type: RIBOSOME / Entity ID: #1-#55 / Source: NATURAL |
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| 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: 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: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
| CTF correction | Details: Relion / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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| 3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 12156 / Symmetry type: POINT |
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Homo sapiens (human)
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FIELD EMISSION GUN