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Yorodumi- EMDB-36945: Cryo-EM structure of the yeast 80S ribosome with tigecycline, Not... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36945 | |||||||||
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Title | Cryo-EM structure of the yeast 80S ribosome with tigecycline, Not5 and P-site tRNA | |||||||||
Map data | filtered by Deepemhancer | |||||||||
Sample |
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Keywords | 80S ribosome / tigecycline / antibiotic / RIBOSOME | |||||||||
Function / homology | Function and homology information deadenylation-independent decapping of nuclear-transcribed mRNA / CCR4-NOT core complex / nuclear-transcribed mRNA poly(A) tail shortening / deadenylation-dependent decapping of nuclear-transcribed mRNA / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, LSU-rRNA,5S) / negative regulation of glucose mediated signaling pathway / negative regulation of translational frameshifting / Negative regulators of DDX58/IFIH1 signaling / Protein methylation / positive regulation of translational fidelity ...deadenylation-independent decapping of nuclear-transcribed mRNA / CCR4-NOT core complex / nuclear-transcribed mRNA poly(A) tail shortening / deadenylation-dependent decapping of nuclear-transcribed mRNA / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, LSU-rRNA,5S) / negative regulation of glucose mediated signaling pathway / negative regulation of translational frameshifting / Negative regulators of DDX58/IFIH1 signaling / Protein methylation / positive regulation of translational fidelity / RMTs methylate histone arginines / mTORC1-mediated signalling / Protein hydroxylation / ribosome-associated ubiquitin-dependent protein catabolic process / GDP-dissociation inhibitor activity / nonfunctional rRNA decay / positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay / pre-mRNA 5'-splice site binding / Formation of the ternary complex, and subsequently, the 43S complex / Translation initiation complex formation / preribosome, small subunit precursor / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Ribosomal scanning and start codon recognition / response to cycloheximide / mRNA destabilization / Major pathway of rRNA processing in the nucleolus and cytosol / SRP-dependent cotranslational protein targeting to membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Formation of a pool of free 40S subunits / negative regulation of mRNA splicing, via spliceosome / regulation of amino acid metabolic process / preribosome, large subunit precursor / L13a-mediated translational silencing of Ceruloplasmin expression / translational elongation / ribosomal large subunit export from nucleus / G-protein alpha-subunit binding / positive regulation of protein kinase activity / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / Ub-specific processing proteases / regulation of translational fidelity / protein-RNA complex assembly / ribosomal subunit export from nucleus / ribosomal small subunit export from nucleus / translation regulator activity / translational termination / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / DNA-(apurinic or apyrimidinic site) endonuclease activity / maturation of LSU-rRNA / cellular response to amino acid starvation / rescue of stalled ribosome / ribosome assembly / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / translational initiation / positive regulation of transcription elongation by RNA polymerase II / macroautophagy / protein kinase C binding / transcription elongation by RNA polymerase II / P-body / maintenance of translational fidelity / cytoplasmic stress granule / modification-dependent protein catabolic process / rRNA processing / protein tag activity / ribosomal small subunit biogenesis / ribosome biogenesis / small ribosomal subunit rRNA binding / ribosome binding / ribosomal large subunit assembly / ribosomal small subunit assembly / small ribosomal subunit / large ribosomal subunit rRNA binding / 5S rRNA binding / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / negative regulation of translation / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / translation / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / negative regulation of gene expression / response to antibiotic / mRNA binding / ubiquitin protein ligase binding / nucleolus / mitochondrion / RNA binding / zinc ion binding / nucleoplasm / nucleus Similarity search - Function | |||||||||
Biological species | Saccharomyces cerevisiae (brewer's yeast) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Buschauer R / Beckmann R / Cheng J | |||||||||
Funding support | 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36945.map.gz | 372.1 MB | EMDB map data format | |
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Header (meta data) | emd-36945-v30.xml emd-36945.xml | 107 KB 107 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36945_fsc.xml | 17 KB | Display | FSC data file |
Images | emd_36945.png | 147.7 KB | ||
Filedesc metadata | emd-36945.cif.gz | 19.7 KB | ||
Others | emd_36945_additional_1.map.gz emd_36945_additional_2.map.gz emd_36945_half_map_1.map.gz emd_36945_half_map_2.map.gz | 244.5 MB 336.3 MB 337.8 MB 337.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36945 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36945 | HTTPS FTP |
-Validation report
Summary document | emd_36945_validation.pdf.gz | 904.6 KB | Display | EMDB validaton report |
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Full document | emd_36945_full_validation.pdf.gz | 904.2 KB | Display | |
Data in XML | emd_36945_validation.xml.gz | 25 KB | Display | |
Data in CIF | emd_36945_validation.cif.gz | 33 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36945 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36945 | HTTPS FTP |
-Related structure data
Related structure data | 8k82MC 8k2aC 8k2bC 8k2cC 8k2dC 8xsxC 8xsyC 8xszC 8xt0C 8xt1C 8xt2C 8xt3C 8yooC 8yopC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_36945.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | filtered by Deepemhancer | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.847 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: local resolution filtered
File | emd_36945_additional_1.map | ||||||||||||
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Annotation | local resolution filtered | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: consensus map without post process
File | emd_36945_additional_2.map | ||||||||||||
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Annotation | consensus map without post process | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36945_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36945_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : yeast 80S ribosome
+Supramolecule #1: yeast 80S ribosome
+Macromolecule #1: 18S rRNA
+Macromolecule #2: mRNA
+Macromolecule #3: tRNA
+Macromolecule #4: 23S rRNA
+Macromolecule #5: 5S rRNA
+Macromolecule #6: 5.8S rRNA
+Macromolecule #7: Small ribosomal subunit protein uS2A
+Macromolecule #8: 40S ribosomal protein S1-A
+Macromolecule #9: 40S ribosomal protein S2
+Macromolecule #10: Small ribosomal subunit protein uS3
+Macromolecule #11: 40S ribosomal protein S4-A
+Macromolecule #12: Small ribosomal subunit protein uS7
+Macromolecule #13: 40S ribosomal protein S6-A
+Macromolecule #14: 40S ribosomal protein S7-A
+Macromolecule #15: 40S ribosomal protein S8-A
+Macromolecule #16: 40S ribosomal protein S9-A
+Macromolecule #17: Small ribosomal subunit protein eS10A
+Macromolecule #18: Small ribosomal subunit protein uS17A
+Macromolecule #19: Small ribosomal subunit protein eS12
+Macromolecule #20: 40S ribosomal protein S13
+Macromolecule #21: 40S ribosomal protein S14-A
+Macromolecule #22: Small ribosomal subunit protein uS19
+Macromolecule #23: Small ribosomal subunit protein uS9A
+Macromolecule #24: Small ribosomal subunit protein eS17A
+Macromolecule #25: Small ribosomal subunit protein uS13A
+Macromolecule #26: Small ribosomal subunit protein eS19A
+Macromolecule #27: Small ribosomal subunit protein uS10
+Macromolecule #28: Small ribosomal subunit protein eS21A
+Macromolecule #29: 40S ribosomal protein S22-A
+Macromolecule #30: 40S ribosomal protein S23-A
+Macromolecule #31: 40S ribosomal protein S24-A
+Macromolecule #32: Small ribosomal subunit protein eS25A
+Macromolecule #33: Small ribosomal subunit protein eS26B
+Macromolecule #34: 40S ribosomal protein S27-A
+Macromolecule #35: Small ribosomal subunit protein eS28A
+Macromolecule #36: Small ribosomal subunit protein uS14A
+Macromolecule #37: 40S ribosomal protein S30-A
+Macromolecule #38: Ubiquitin-ribosomal protein eS31 fusion protein
+Macromolecule #39: Small ribosomal subunit protein RACK1
+Macromolecule #40: Large ribosomal subunit protein uL2A
+Macromolecule #41: Large ribosomal subunit protein uL3
+Macromolecule #42: Large ribosomal subunit protein uL4A
+Macromolecule #43: Large ribosomal subunit protein uL18
+Macromolecule #44: Large ribosomal subunit protein eL6A
+Macromolecule #45: Large ribosomal subunit protein uL30A
+Macromolecule #46: Large ribosomal subunit protein eL8A
+Macromolecule #47: Large ribosomal subunit protein uL6A
+Macromolecule #48: Large ribosomal subunit protein uL16
+Macromolecule #49: Large ribosomal subunit protein uL5A
+Macromolecule #50: Large ribosomal subunit protein uL11A
+Macromolecule #51: Large ribosomal subunit protein eL13A
+Macromolecule #52: Large ribosomal subunit protein eL14A
+Macromolecule #53: Large ribosomal subunit protein eL15A
+Macromolecule #54: Large ribosomal subunit protein uL13A
+Macromolecule #55: Large ribosomal subunit protein uL22A
+Macromolecule #56: Large ribosomal subunit protein eL18A
+Macromolecule #57: Large ribosomal subunit protein eL19A
+Macromolecule #58: Large ribosomal subunit protein eL20A
+Macromolecule #59: Large ribosomal subunit protein eL21A
+Macromolecule #60: Large ribosomal subunit protein eL22A
+Macromolecule #61: Large ribosomal subunit protein uL14A
+Macromolecule #62: Large ribosomal subunit protein eL24A
+Macromolecule #63: Large ribosomal subunit protein uL23
+Macromolecule #64: Large ribosomal subunit protein uL24A
+Macromolecule #65: Large ribosomal subunit protein eL27A
+Macromolecule #66: Large ribosomal subunit protein uL15
+Macromolecule #67: Large ribosomal subunit protein eL29
+Macromolecule #68: Large ribosomal subunit protein eL30
+Macromolecule #69: Large ribosomal subunit protein eL31A
+Macromolecule #70: Large ribosomal subunit protein eL32
+Macromolecule #71: Large ribosomal subunit protein eL33A
+Macromolecule #72: Large ribosomal subunit protein eL34A
+Macromolecule #73: Large ribosomal subunit protein uL29A
+Macromolecule #74: Large ribosomal subunit protein eL36A
+Macromolecule #75: Large ribosomal subunit protein eL37A
+Macromolecule #76: Large ribosomal subunit protein eL38
+Macromolecule #77: Large ribosomal subunit protein eL39
+Macromolecule #78: Ubiquitin-ribosomal protein eL40A fusion protein
+Macromolecule #79: Large ribosomal subunit protein eL41A
+Macromolecule #80: Large ribosomal subunit protein eL42A
+Macromolecule #81: Large ribosomal subunit protein eL43A
+Macromolecule #82: Large ribosomal subunit protein uL1A
+Macromolecule #83: Large ribosomal subunit protein uL10
+Macromolecule #84: General negative regulator of transcription subunit 5
+Macromolecule #85: MAGNESIUM ION
+Macromolecule #86: TIGECYCLINE
+Macromolecule #87: SPERMIDINE
+Macromolecule #88: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 44.0 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: 3.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |