[English] 日本語
Yorodumi- EMDB-36837: Cryo-EM structure of the human 39S mitoribosome with Tigecycline -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36837 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the human 39S mitoribosome with Tigecycline | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | 39S mitoribosome / Tigecycline / antibiotic / RIBOSOME | |||||||||
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 | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Li X / Wang M / Cheng J | |||||||||
Funding support | 1 items
| |||||||||
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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_36837.map.gz | 225.8 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-36837-v30.xml emd-36837.xml | 72.1 KB 72.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36837_fsc.xml | 14.8 KB | Display | FSC data file |
Images | emd_36837.png | 122.4 KB | ||
Filedesc metadata | emd-36837.cif.gz | 15.2 KB | ||
Others | emd_36837_half_map_1.map.gz emd_36837_half_map_2.map.gz | 226 MB 225.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36837 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36837 | HTTPS FTP |
-Validation report
Summary document | emd_36837_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_36837_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_36837_validation.xml.gz | 21.6 KB | Display | |
Data in CIF | emd_36837_validation.cif.gz | 27.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36837 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36837 | HTTPS FTP |
-Related structure data
Related structure data | 8k2bMC 8k2aC 8k2cC 8k2dC 8k82C 8xsxC 8xsyC 8xszC 8xt0C 8xt1C 8xt2C 8xt3C 8yooC 8yopC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_36837.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.19 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: consensus map
File | emd_36837_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | consensus map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_36837_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
+Entire : 55S mitoribosome with tigecycline
+Supramolecule #1: 55S mitoribosome with tigecycline
+Macromolecule #1: 16s rRNA
+Macromolecule #2: Val tRNA
+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: Mitochondrial assembly of ribosomal large subunit protein 1
+Macromolecule #54: Mitochondrial ribosome and complex I assembly factor AltMIEF1
+Macromolecule #55: Acyl carrier protein, mitochondrial
+Macromolecule #56: MAGNESIUM ION
+Macromolecule #57: TIGECYCLINE
+Macromolecule #58: ZINC ION
+Macromolecule #59: 4'-PHOSPHOPANTETHEINE
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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: FIELD EMISSION GUN |
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 |