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- EMDB-19460: Human mitochondrial ribosome in complex with antibiotic tigecycline -
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Open data
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Basic information
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Title | Human mitochondrial ribosome in complex with antibiotic tigecycline | |||||||||
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![]() | antibiotics / immunometabolism / mitochondrial ribosomes / tetracyclines / T cells. / RIBOSOME | |||||||||
Function / homology | ![]() rRNA import into mitochondrion / mitochondrial translational termination / mitochondrial translational elongation / mitochondrial ribosome assembly / translation release factor activity, codon nonspecific / Mitochondrial translation elongation / Mitochondrial translation termination / Mitochondrial translation initiation / translation release factor activity / mitochondrial large ribosomal subunit ...rRNA import into mitochondrion / mitochondrial translational termination / mitochondrial translational elongation / mitochondrial ribosome assembly / translation release factor activity, codon nonspecific / Mitochondrial translation elongation / Mitochondrial translation termination / Mitochondrial translation initiation / translation release factor activity / mitochondrial large ribosomal subunit / negative regulation of mitotic nuclear division / 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 / ribosome / structural constituent of ribosome / mitochondrial matrix / protein domain specific binding / translation / 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 | single particle reconstruction / cryo EM / Resolution: 2.4 Å | |||||||||
![]() | Khawaja A / Nguyen MD / Singh V / 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. | |||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 56.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 110.3 KB 110.3 KB | Display Display | ![]() |
Images | ![]() | 76.2 KB | ||
Filedesc metadata | ![]() | 22.9 KB | ||
Others | ![]() | 257.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 404.7 KB | Display | ![]() |
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Full document | ![]() | 404.2 KB | Display | |
Data in XML | ![]() | 8.1 KB | Display | |
Data in CIF | ![]() | 9.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8rriMC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.01 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: consensus P-tRNA Homogenous refinement
File | emd_19460_additional_1.map | ||||||||||||
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Annotation | consensus P-tRNA Homogenous refinement | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Human mitochondrial ribosome in complex with antibiotic tigecycline
+Supramolecule #1: Human mitochondrial ribosome in complex with antibiotic tigecycline
+Macromolecule #1: mitochondrial tRNAVal
+Macromolecule #82: E/E-tRNA
+Macromolecule #83: 12S mitochondrial rRNA
+Macromolecule #84: 16S mitochondrial rRNA
+Macromolecule #85: mRNA
+Macromolecule #86: P/P-tRNA
+Macromolecule #2: 39S ribosomal protein L2, mitochondrial
+Macromolecule #3: 39S ribosomal protein L3, mitochondrial
+Macromolecule #4: 39S ribosomal protein L4, mitochondrial
+Macromolecule #5: 39S ribosomal protein L9, mitochondrial
+Macromolecule #6: 39S ribosomal protein L11, mitochondrial
+Macromolecule #7: Large ribosomal subunit protein uL13m
+Macromolecule #8: 39S ribosomal protein L14, mitochondrial
+Macromolecule #9: 39S ribosomal protein L15, mitochondrial
+Macromolecule #10: 39S ribosomal protein L16, mitochondrial
+Macromolecule #11: 39S ribosomal protein L17, mitochondrial
+Macromolecule #12: 39S ribosomal protein L18, mitochondrial
+Macromolecule #13: 39S ribosomal protein L19, mitochondrial
+Macromolecule #14: 39S ribosomal protein L20, mitochondrial
+Macromolecule #15: 39S ribosomal protein L21, mitochondrial
+Macromolecule #16: 39S ribosomal protein L22, mitochondrial
+Macromolecule #17: Large ribosomal subunit protein uL23m
+Macromolecule #18: 39S ribosomal protein L24, mitochondrial
+Macromolecule #19: 39S ribosomal protein L27, mitochondrial
+Macromolecule #20: 39S ribosomal protein L28, mitochondrial
+Macromolecule #21: 39S ribosomal protein L47, mitochondrial
+Macromolecule #22: 39S ribosomal protein L30, mitochondrial
+Macromolecule #23: 39S ribosomal protein L32, mitochondrial
+Macromolecule #24: 39S ribosomal protein L33, mitochondrial
+Macromolecule #25: 39S ribosomal protein L34, mitochondrial
+Macromolecule #26: 39S ribosomal protein L35, mitochondrial
+Macromolecule #27: 39S ribosomal protein L36, mitochondrial
+Macromolecule #28: 39S ribosomal protein L1, mitochondrial
+Macromolecule #29: 39S ribosomal protein L37, mitochondrial
+Macromolecule #30: 39S ribosomal protein L38, mitochondrial
+Macromolecule #31: 39S ribosomal protein L39, mitochondrial
+Macromolecule #32: 39S ribosomal protein L40, mitochondrial
+Macromolecule #33: 39S ribosomal protein L41, mitochondrial
+Macromolecule #34: 39S ribosomal protein L42, mitochondrial
+Macromolecule #35: 39S ribosomal protein L43, mitochondrial
+Macromolecule #36: 39S ribosomal protein L44, mitochondrial
+Macromolecule #37: 39S ribosomal protein L45, mitochondrial
+Macromolecule #38: 39S ribosomal protein L46, mitochondrial
+Macromolecule #39: 39S ribosomal protein L48, mitochondrial
+Macromolecule #40: 39S ribosomal protein L49, mitochondrial
+Macromolecule #41: 39S ribosomal protein L50, mitochondrial
+Macromolecule #42: 39S ribosomal protein L51, mitochondrial
+Macromolecule #43: 39S ribosomal protein L52, mitochondrial
+Macromolecule #44: Large ribosomal subunit protein mL53
+Macromolecule #45: 39S ribosomal protein L54, mitochondrial
+Macromolecule #46: 39S ribosomal protein L55, mitochondrial
+Macromolecule #47: Ribosomal protein 63, mitochondrial
+Macromolecule #48: Peptidyl-tRNA hydrolase ICT1, mitochondrial
+Macromolecule #49: Growth arrest and DNA damage-inducible proteins-interacting protein 1
+Macromolecule #50: 39S ribosomal protein S18a, mitochondrial
+Macromolecule #51: 39S ribosomal protein S30, mitochondrial
+Macromolecule #52: 28S ribosomal protein S2, mitochondrial
+Macromolecule #53: 28S ribosomal protein S24, mitochondrial
+Macromolecule #54: 28S ribosomal protein S5, mitochondrial
+Macromolecule #55: 28S ribosomal protein S6, mitochondrial
+Macromolecule #56: 28S ribosomal protein S7, mitochondrial
+Macromolecule #57: 28S ribosomal protein S9, mitochondrial
+Macromolecule #58: 28S ribosomal protein S10, mitochondrial
+Macromolecule #59: 28S ribosomal protein S11, mitochondrial
+Macromolecule #60: 28S ribosomal protein S12, mitochondrial
+Macromolecule #61: 28S ribosomal protein S14, mitochondrial
+Macromolecule #62: 28S ribosomal protein S15, mitochondrial
+Macromolecule #63: 28S ribosomal protein S16, mitochondrial
+Macromolecule #64: 28S ribosomal protein S17, mitochondrial
+Macromolecule #65: 28S ribosomal protein S18b, mitochondrial
+Macromolecule #66: 28S ribosomal protein S18c, mitochondrial
+Macromolecule #67: Small ribosomal subunit protein bS21m
+Macromolecule #68: 28S ribosomal protein S22, mitochondrial
+Macromolecule #69: 28S ribosomal protein S23, mitochondrial
+Macromolecule #70: Small ribosomal subunit protein mS25
+Macromolecule #71: 28S ribosomal protein S26, mitochondrial
+Macromolecule #72: 28S ribosomal protein S27, mitochondrial
+Macromolecule #73: 28S ribosomal protein S28, mitochondrial
+Macromolecule #74: 28S ribosomal protein S29, mitochondrial
+Macromolecule #75: 28S ribosomal protein S31, mitochondrial
+Macromolecule #76: 28S ribosomal protein S33, mitochondrial
+Macromolecule #77: 28S ribosomal protein S34, mitochondrial
+Macromolecule #78: 28S ribosomal protein S35, mitochondrial
+Macromolecule #79: Small ribosomal subunit protein mS37
+Macromolecule #80: Aurora kinase A-interacting protein
+Macromolecule #81: Pentatricopeptide repeat domain-containing protein 3, mitochondrial
+Macromolecule #87: VALINE
+Macromolecule #88: MAGNESIUM ION
+Macromolecule #89: FE2/S2 (INORGANIC) CLUSTER
+Macromolecule #90: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #91: GUANOSINE-5'-DIPHOSPHATE
+Macromolecule #92: TIGECYCLINE
+Macromolecule #93: POTASSIUM ION
+Macromolecule #94: water
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.4 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |