+Open data
-Basic information
Entry | Database: PDB / ID: 8k2b | ||||||
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Title | Cryo-EM structure of the human 39S mitoribosome with Tigecycline | ||||||
Components |
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Keywords | RIBOSOME / 39S mitoribosome / Tigecycline / antibiotic | ||||||
Function / homology | Function and homology information negative regulation of mitochondrial translation / mitochondrial large ribosomal subunit assembly / Complex I biogenesis / negative regulation of ribosome biogenesis / protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Protein lipoylation / mitochondrial [2Fe-2S] assembly complex / Respiratory electron transport / mitochondrial translational termination ...negative regulation of mitochondrial translation / mitochondrial large ribosomal subunit assembly / Complex I biogenesis / negative regulation of ribosome biogenesis / protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Protein lipoylation / mitochondrial [2Fe-2S] assembly complex / Respiratory electron transport / mitochondrial translational termination / mitochondrial translational elongation / translation release factor activity, codon nonspecific / microprocessor complex / Mitochondrial translation elongation / Mitochondrial translation termination / positive regulation of mitochondrial translation / Mitochondrial translation initiation / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / mitochondrial fission / mitochondrial large ribosomal subunit / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / peptidyl-tRNA hydrolase / mitochondrial small ribosomal subunit / [2Fe-2S] cluster assembly / aminoacyl-tRNA hydrolase activity / respiratory chain complex I / iron-sulfur cluster assembly / mitochondrial ribosome / mitochondrial translation / ribosomal large subunit binding / : / mitochondrial electron transport, NADH to ubiquinone / mitochondrial respiratory chain complex I assembly / proton motive force-driven mitochondrial ATP synthesis / acyl binding / anatomical structure morphogenesis / acyl carrier activity / RNA processing / Mitochondrial protein degradation / aerobic respiration / rescue of stalled ribosome / ribosomal large subunit biogenesis / cellular response to leukemia inhibitory factor / fatty acid binding / mitochondrial membrane / fibrillar center / fatty acid biosynthetic process / double-stranded RNA binding / large ribosomal subunit / small ribosomal subunit rRNA binding / cell junction / large ribosomal subunit rRNA binding / 5S rRNA binding / endonuclease activity / mitochondrial inner membrane / negative regulation of translation / nuclear body / rRNA binding / ribosome / structural constituent of ribosome / mitochondrial matrix / ribonucleoprotein complex / translation / protein domain specific binding / nucleotide binding / mRNA binding / calcium ion binding / synapse / nucleolus / apoptotic process / 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: 2024 Title: 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-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
Summary document | 8k2b_validation.pdf.gz | 2.1 MB | Display | wwPDB validaton report |
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Full document | 8k2b_full_validation.pdf.gz | 2.1 MB | Display | |
Data in XML | 8k2b_validation.xml.gz | 223.3 KB | Display | |
Data in CIF | 8k2b_validation.cif.gz | 372.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k2/8k2b ftp://data.pdbj.org/pub/pdb/validation_reports/k2/8k2b | HTTPS FTP |
-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 (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
-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 |
-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 |
-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) |
-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 |