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- EMDB-36836: Cryo-EM structure of the human 55S mitoribosome with Tigecycline -
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Open data
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Basic information
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Title | Cryo-EM structure of the human 55S mitoribosome with Tigecycline | |||||||||
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![]() | 55S mitoribosome / Tigecycline / antibiotic / RIBOSOME | |||||||||
Function / homology | ![]() mitochondrial ribosome binding / mitochondrial translational elongation / mitochondrial translational termination / mitochondrial ribosome assembly / microprocessor complex / translation release factor activity, codon nonspecific / Mitochondrial translation elongation / Mitochondrial translation termination / positive regulation of mitochondrial translation / Mitochondrial translation initiation ...mitochondrial ribosome binding / mitochondrial translational elongation / mitochondrial translational termination / mitochondrial ribosome assembly / microprocessor complex / translation release factor activity, codon nonspecific / Mitochondrial translation elongation / Mitochondrial translation termination / positive regulation of mitochondrial translation / Mitochondrial translation initiation / negative regulation of mitotic nuclear division / mitochondrial large ribosomal subunit / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / peptidyl-tRNA hydrolase / mitochondrial small ribosomal subunit / aminoacyl-tRNA hydrolase activity / mitochondrial ribosome / mitochondrial translation / positive regulation of proteolysis / ribosomal small subunit binding / anatomical structure morphogenesis / RNA processing / rescue of stalled ribosome / cellular response to leukemia inhibitory factor / Mitochondrial protein degradation / apoptotic signaling pathway / fibrillar center / cell junction / large ribosomal subunit / double-stranded RNA binding / regulation of translation / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / nuclear membrane / 5S rRNA binding / large ribosomal subunit rRNA binding / endonuclease activity / cytosolic large ribosomal subunit / cell population proliferation / tRNA binding / nuclear body / rRNA binding / negative regulation of translation / mitochondrial inner membrane / ribosome / structural constituent of ribosome / mitochondrial matrix / translation / ribonucleoprotein complex / protein domain specific binding / intracellular membrane-bounded organelle / mRNA binding / nucleotide binding / synapse / nucleolus / GTP binding / apoptotic process / mitochondrion / RNA binding / nucleoplasm / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
![]() | Li X / Wang M / Cheng J | |||||||||
Funding support | 1 items
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![]() | ![]() 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 159 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 111.5 KB 111.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.8 KB | Display | ![]() |
Images | ![]() | 176.1 KB | ||
Filedesc metadata | ![]() | 21.3 KB | ||
Others | ![]() ![]() ![]() ![]() ![]() ![]() | 158.6 MB 155 MB 159.5 MB 253.6 MB 225.3 MB 225.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 879 KB | Display | ![]() |
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Full document | ![]() | 878.5 KB | Display | |
Data in XML | ![]() | 21.6 KB | Display | |
Data in CIF | ![]() | 27.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8k2aMC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yooC ![]() 8yopC M: atomic model generated by this map C: citing same article ( |
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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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Voxel size | X=Y=Z: 1.19 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: focus on 28S body
File | emd_36836_additional_1.map | ||||||||||||
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Annotation | focus on 28S body | ||||||||||||
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Density Histograms |
-Additional map: focus on 28S head
File | emd_36836_additional_2.map | ||||||||||||
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Annotation | focus on 28S head | ||||||||||||
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Density Histograms |
-Additional map: focus on 39S ribosome
File | emd_36836_additional_3.map | ||||||||||||
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Annotation | focus on 39S ribosome | ||||||||||||
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-Additional map: deepemhancer
File | emd_36836_additional_4.map | ||||||||||||
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Annotation | deepemhancer | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_36836_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36836_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
+Entire : 55S mitoribosome with tigecycline
+Supramolecule #1: 55S mitoribosome with tigecycline
+Macromolecule #1: 16S rRNA
+Macromolecule #2: Val tRNA
+Macromolecule #83: 12S rRNA
+Macromolecule #3: Large ribosomal subunit protein uL2m
+Macromolecule #4: Large ribosomal subunit protein uL3m
+Macromolecule #5: Large ribosomal subunit protein uL4m
+Macromolecule #6: Large ribosomal subunit protein bL9m
+Macromolecule #7: Large ribosomal subunit protein uL10m
+Macromolecule #8: Large ribosomal subunit protein uL11m
+Macromolecule #9: Large ribosomal subunit protein uL13m
+Macromolecule #10: Large ribosomal subunit protein uL14m
+Macromolecule #11: Large ribosomal subunit protein uL15m
+Macromolecule #12: Large ribosomal subunit protein uL16m
+Macromolecule #13: Large ribosomal subunit protein bL17m
+Macromolecule #14: Mitochondrial ribosomal protein L18, isoform CRA_b
+Macromolecule #15: Large ribosomal subunit protein bL19m
+Macromolecule #16: Large ribosomal subunit protein bL20m
+Macromolecule #17: Large ribosomal subunit protein bL21m
+Macromolecule #18: 39S ribosomal protein L22, mitochondrial
+Macromolecule #19: Large ribosomal subunit protein uL23m
+Macromolecule #20: Large ribosomal subunit protein uL24m
+Macromolecule #21: Large ribosomal subunit protein bL27m
+Macromolecule #22: Large ribosomal subunit protein bL28m
+Macromolecule #23: Large ribosomal subunit protein uL29m
+Macromolecule #24: Large ribosomal subunit protein uL30m
+Macromolecule #25: Large ribosomal subunit protein bL32m
+Macromolecule #26: Large ribosomal subunit protein bL33m
+Macromolecule #27: Large ribosomal subunit protein bL34m
+Macromolecule #28: Large ribosomal subunit protein bL35m
+Macromolecule #29: Large ribosomal subunit protein bL36m
+Macromolecule #30: Large ribosomal subunit protein mL37
+Macromolecule #31: Large ribosomal subunit protein mL38
+Macromolecule #32: Large ribosomal subunit protein mL39
+Macromolecule #33: Large ribosomal subunit protein mL40
+Macromolecule #34: Large ribosomal subunit protein mL41
+Macromolecule #35: Large ribosomal subunit protein mL42
+Macromolecule #36: Large ribosomal subunit protein mL43
+Macromolecule #37: Large ribosomal subunit protein mL44
+Macromolecule #38: Large ribosomal subunit protein mL45
+Macromolecule #39: Large ribosomal subunit protein mL46
+Macromolecule #40: Large ribosomal subunit protein mL48
+Macromolecule #41: Large ribosomal subunit protein mL49
+Macromolecule #42: Large ribosomal subunit protein mL50
+Macromolecule #43: Large ribosomal subunit protein mL51
+Macromolecule #44: 39S ribosomal protein L52, mitochondrial
+Macromolecule #45: Large ribosomal subunit protein mL53
+Macromolecule #46: Large ribosomal subunit protein mL54
+Macromolecule #47: Large ribosomal subunit protein mL55
+Macromolecule #48: Large ribosomal subunit protein mL63
+Macromolecule #49: Large ribosomal subunit protein mL62
+Macromolecule #50: Large ribosomal subunit protein mL64
+Macromolecule #51: Large ribosomal subunit protein mL66
+Macromolecule #52: Large ribosomal subunit protein mL65
+Macromolecule #53: Small ribosomal subunit protein uS2m
+Macromolecule #54: Small ribosomal subunit protein uS3m
+Macromolecule #55: Small ribosomal subunit protein uS5m
+Macromolecule #56: Small ribosomal subunit protein bS6m
+Macromolecule #57: Small ribosomal subunit protein uS7m
+Macromolecule #58: Small ribosomal subunit protein uS9m
+Macromolecule #59: Small ribosomal subunit protein uS10m
+Macromolecule #60: Small ribosomal subunit protein uS11m
+Macromolecule #61: Small ribosomal subunit protein uS12m
+Macromolecule #62: Small ribosomal subunit protein uS14m
+Macromolecule #63: Small ribosomal subunit protein uS15m
+Macromolecule #64: Small ribosomal subunit protein bS16m
+Macromolecule #65: Small ribosomal subunit protein uS17m
+Macromolecule #66: Small ribosomal subunit protein mS40
+Macromolecule #67: Small ribosomal subunit protein bS18m
+Macromolecule #68: Small ribosomal subunit protein bS21m
+Macromolecule #69: Small ribosomal subunit protein mS22
+Macromolecule #70: Small ribosomal subunit protein mS23
+Macromolecule #71: Small ribosomal subunit protein mS25
+Macromolecule #72: Small ribosomal subunit protein mS26
+Macromolecule #73: Small ribosomal subunit protein mS27
+Macromolecule #74: Small ribosomal subunit protein bS1m
+Macromolecule #75: Small ribosomal subunit protein mS29
+Macromolecule #76: Small ribosomal subunit protein mS31
+Macromolecule #77: Small ribosomal subunit protein mS33
+Macromolecule #78: Small ribosomal subunit protein mS34
+Macromolecule #79: Small ribosomal subunit protein mS35
+Macromolecule #80: Small ribosomal subunit protein mS37
+Macromolecule #81: Small ribosomal subunit protein mS38
+Macromolecule #82: Small ribosomal subunit protein mS39
+Macromolecule #84: MAGNESIUM ION
+Macromolecule #85: TIGECYCLINE
+Macromolecule #86: ZINC ION
+Macromolecule #87: GUANOSINE-5'-DIPHOSPHATE
-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: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |