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- PDB-8rri: Human mitochondrial ribosome in complex with antibiotic tigecycline -
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Open data
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Basic information
Entry | Database: PDB / ID: 8rri | ||||||||||||||||||
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Title | Human mitochondrial ribosome in complex with antibiotic tigecycline | ||||||||||||||||||
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![]() | RIBOSOME / antibiotics / immunometabolism / mitochondrial ribosomes / tetracyclines / T cells. | ||||||||||||||||||
Function / homology | ![]() rRNA import into mitochondrion / mitochondrial translational termination / mitochondrial ribosome assembly / mitochondrial translational elongation / Mitochondrial translation elongation / Mitochondrial translation termination / translation release factor activity, codon nonspecific / Mitochondrial translation initiation / translation release factor activity / negative regulation of mitotic nuclear division ...rRNA import into mitochondrion / mitochondrial translational termination / mitochondrial ribosome assembly / mitochondrial translational elongation / Mitochondrial translation elongation / Mitochondrial translation termination / translation release factor activity, codon nonspecific / Mitochondrial translation initiation / translation release factor activity / negative regulation of mitotic nuclear division / mitochondrial large ribosomal subunit / peptidyl-tRNA hydrolase / mitochondrial ribosome / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / mitochondrial small ribosomal subunit / peptidyl-tRNA hydrolase activity / mitochondrial translation / positive regulation of proteolysis / ribosomal small subunit binding / anatomical structure morphogenesis / RNA processing / rescue of stalled ribosome / Mitochondrial protein degradation / cellular response to leukemia inhibitory factor / apoptotic signaling pathway / fibrillar center / cell junction / regulation of translation / double-stranded RNA binding / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / large ribosomal subunit rRNA binding / small ribosomal subunit rRNA binding / endonuclease activity / nuclear membrane / tRNA binding / cell population proliferation / mitochondrial inner membrane / negative regulation of translation / rRNA binding / nuclear body / structural constituent of ribosome / ribosome / mitochondrial matrix / translation / protein domain specific binding / ribonucleoprotein complex / nucleotide binding / intracellular membrane-bounded organelle / mRNA binding / apoptotic process / GTP binding / nucleolus / mitochondrion / extracellular space / RNA binding / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.4 Å | ||||||||||||||||||
![]() | Khawaja, A. / Sing, V. / Nguyen, M.D. / Rorbach, J. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: T cell toxicity induced by tigecycline binding to the mitochondrial ribosome. Authors: Qiuya Shao / Anas Khawaja / Minh Duc Nguyen / Vivek Singh / Jingdian Zhang / Yong Liu / Joel Nordin / Monika Adori / C Axel Innis / Xaquin Castro Dopico / Joanna Rorbach / ![]() ![]() ![]() ![]() ![]() Abstract: Tetracyclines are essential bacterial protein synthesis inhibitors under continual development to combat antibiotic resistance yet suffer from unwanted side effects. Mitoribosomes - responsible for ...Tetracyclines are essential bacterial protein synthesis inhibitors under continual development to combat antibiotic resistance yet suffer from unwanted side effects. Mitoribosomes - responsible for generating oxidative phosphorylation (OXPHOS) subunits - share structural similarities with bacterial machinery and may suffer from cross-reactivity. Since lymphocytes rely upon OXPHOS upregulation to establish immunity, we set out to assess the impact of ribosome-targeting antibiotics on human T cells. We find tigecycline, a third-generation tetracycline, to be the most cytotoxic compound tested. In vitro, 5-10 μM tigecycline inhibits mitochondrial but not cytosolic translation, mitochondrial complex I, III and IV expression, and curtails the activation and expansion of unique T cell subsets. By cryo-EM, we find tigecycline to occupy three sites on T cell mitoribosomes. In addition to the conserved A-site found in bacteria, tigecycline also attaches to the peptidyl transferase center of the large subunit. Furthermore, a third, distinct binding site on the large subunit, aligns with helices analogous to those in bacteria, albeit lacking methylation in humans. The data provide a mechanism to explain part of the anti-inflammatory effects of these drugs and inform antibiotic design. | ||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 7.4 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.7 MB | Display | ![]() |
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Full document | ![]() | 1.8 MB | Display | |
Data in XML | ![]() | 345.1 KB | Display | |
Data in CIF | ![]() | 614 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 19460MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-RNA chain , 6 types, 6 molecules BAyAAAAzAx
#1: RNA chain | Mass: 22989.752 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#82: RNA chain | Mass: 16669.957 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#83: RNA chain | Mass: 306218.312 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#84: RNA chain | Mass: 499786.438 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#85: RNA chain | Mass: 10230.085 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#86: RNA chain | Mass: 22353.307 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+39S ribosomal protein ... , 44 types, 44 molecules DEFHJLMNOPQRSTVWXYZ01234z56789...
-Large ribosomal subunit protein ... , 3 types, 3 molecules KUk
#7: Protein | Mass: 20617.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#17: Protein | Mass: 17702.029 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#44: Protein | Mass: 12020.701 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 5 types, 5 molecules opqA3A4
#47: Protein | Mass: 12292.333 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#48: Protein | Mass: 23674.203 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#49: Protein | Mass: 25426.895 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#80: Protein | Mass: 22395.326 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#81: Protein | Mass: 78648.547 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+28S ribosomal protein ... , 25 types, 25 molecules ABACADAEAFAGAHAIAJAKALAMANAOAPARASAUAVAWAXAYAZA0A1
-Small ribosomal subunit protein ... , 3 types, 3 molecules AQATA2
#67: Protein | Mass: 10659.494 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#70: Protein | Mass: 19717.045 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#79: Protein | Mass: 13393.661 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 8 types, 1089 molecules 














#87: Chemical | ChemComp-VAL / | ||||||||||||
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#88: Chemical | ChemComp-MG / #89: Chemical | #90: Chemical | ChemComp-ATP / | #91: Chemical | ChemComp-GDP / | #92: Chemical | #93: Chemical | ChemComp-K / #94: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-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: Human mitochondrial ribosome in complex with antibiotic tigecycline Type: CELL Entity ID: #2-#49, #51-#65, #67-#69, #71-#73, #75-#82, #85-#86 Source: NATURAL |
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Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.5 |
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: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 400 nm |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: PHENIX / Version: 1.20.1_4487: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 266550 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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