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- PDB-8k2d: Cryo-EM structure of the yeast 80S ribosome with tigecycline, eEF... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8k2d | ||||||
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Title | Cryo-EM structure of the yeast 80S ribosome with tigecycline, eEF2, Stm1 and eIF5A | ||||||
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![]() | RIBOSOME / 80S ribosome / tigecycline / antibiotic | ||||||
Function / homology | ![]() positive regulation of cytoplasmic translational elongation through polyproline stretches / Hypusine synthesis from eIF5A-lysine / CAT tailing / translational frameshifting / Peptide chain elongation / Synthesis of diphthamide-EEF2 / positive regulation of translational termination / triplex DNA binding / ribosome hibernation / translation elongation factor binding ...positive regulation of cytoplasmic translational elongation through polyproline stretches / Hypusine synthesis from eIF5A-lysine / CAT tailing / translational frameshifting / Peptide chain elongation / Synthesis of diphthamide-EEF2 / positive regulation of translational termination / triplex DNA binding / ribosome hibernation / translation elongation factor binding / regulation of translational initiation in response to stress / Platelet degranulation / positive regulation of translational elongation / 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 / positive regulation of translational fidelity / Protein methylation / RMTs methylate histone arginines / mTORC1-mediated signalling / Protein hydroxylation / ribosome-associated ubiquitin-dependent protein catabolic process / GDP-dissociation inhibitor activity / 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 / Ribosomal scanning and start codon recognition / translational elongation / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / preribosome, small subunit precursor / response to cycloheximide / telomeric DNA binding / 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 / Formation of a pool of free 40S subunits / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of mRNA splicing, via spliceosome / L13a-mediated translational silencing of Ceruloplasmin expression / preribosome, large subunit precursor / ribosomal large subunit export from nucleus / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / G-protein alpha-subunit binding / TOR signaling / positive regulation of protein kinase activity / protein-RNA complex assembly / positive regulation of translational initiation / regulation of translational fidelity / Ub-specific processing proteases / ribosomal small subunit export from nucleus / translation regulator activity / translation elongation factor activity / ribosomal subunit export from nucleus / 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) / translation repressor activity / DNA-(apurinic or apyrimidinic site) endonuclease activity / Neutrophil degranulation / translation initiation factor activity / cellular response to amino acid starvation / ribosome assembly / telomere maintenance / rescue of stalled ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of LSU-rRNA / ribosomal large subunit biogenesis / maturation of SSU-rRNA / macroautophagy / small-subunit processome / positive regulation of apoptotic signaling pathway / protein kinase C binding / maintenance of translational fidelity / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / ribosomal large subunit assembly / cytoplasmic stress granule / modification-dependent protein catabolic process / rRNA processing / protein tag activity / ribosome biogenesis / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / protein-folding chaperone binding / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / rRNA binding / negative regulation of translation / ribosome / protein ubiquitination Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Buschauer, R. / Beckmann, R. / Cheng, J. | ||||||
Funding support | 1items
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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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 4.6 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.2 MB | Display | ![]() |
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Full document | ![]() | 2.2 MB | Display | |
Data in XML | ![]() | 360.3 KB | Display | |
Data in CIF | ![]() | 627.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 36839 ![]() 36836 ![]() 36837 ![]() 36838 ![]() 36945 ![]() 38629 ![]() 38630 ![]() 38631 ![]() 38632 ![]() 38633 ![]() 38634 ![]() 38635 ![]() 38636 ![]() 38637 ![]() 38638 ![]() 38639 ![]() 39455 ![]() 39456 ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yooC ![]() 8yopC 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 , 4 types, 4 molecules C2C1C4C3
#1: RNA chain | Mass: 579761.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#2: RNA chain | Mass: 1097493.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#3: RNA chain | Mass: 38951.105 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#4: RNA chain | Mass: 50682.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Small ribosomal subunit protein ... , 18 types, 18 molecules SASDSFSKSLSMSPSQSRSSSTSUSVSZSaScSdSg
#5: Protein | Mass: 28051.330 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#8: Protein | Mass: 26542.789 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#10: Protein | Mass: 25072.600 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#15: Protein | Mass: 12757.445 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#16: Protein | Mass: 17785.934 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#17: Protein | Mass: 15488.631 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#20: Protein | Mass: 16031.907 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#21: Protein | Mass: 15877.490 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#22: Protein | Mass: 15820.413 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#23: Protein | Mass: 17071.641 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#24: Protein | Mass: 15942.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#25: Protein | Mass: 13929.044 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#26: Protein | Mass: 9758.829 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#30: Protein | Mass: 12067.272 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#31: Protein | Mass: 13480.886 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#33: Protein | Mass: 7605.847 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#34: Protein | Mass: 6675.723 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#37: Protein | Mass: 34841.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-40S ribosomal protein ... , 14 types, 14 molecules SBSCSESGSHSISJSNSOSWSXSYSbSe
#6: Protein | Mass: 28798.467 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#7: Protein | Mass: 27490.826 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#9: Protein | Mass: 29469.330 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#11: Protein | Mass: 27054.486 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#12: Protein | Mass: 21658.209 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#13: Protein | Mass: 22537.803 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#14: Protein | Mass: 22487.893 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#18: Protein | Mass: 17059.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#19: Protein | Mass: 14562.655 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#27: Protein | Mass: 14650.062 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#28: Protein | Mass: 16073.896 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#29: Protein | Mass: 15362.848 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#32: Protein | Mass: 8893.391 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#35: Protein | Mass: 7137.541 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Ubiquitin-ribosomal protein ... , 2 types, 2 molecules SfLm
#36: Protein | Mass: 17254.227 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#76: Protein | Mass: 14583.077 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
+Large ribosomal subunit protein ... , 43 types, 43 molecules LALBLCLDLELFLGLHLILJLKLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLd...
-Protein , 3 types, 3 molecules CECDCS
#80: Protein | Mass: 17222.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#83: Protein | Mass: 93407.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P32324, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement |
#84: Protein | Mass: 30048.010 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Non-polymers , 4 types, 20 molecules ![](data/chem/img/ZN.gif)
![](data/chem/img/T1C.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/GDP.gif)
![](data/chem/img/T1C.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/GDP.gif)
#85: Chemical | ChemComp-ZN / #86: Chemical | ChemComp-T1C / #87: Chemical | ChemComp-MG / #88: Chemical | ChemComp-GDP / | |
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-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: yeast 80S ribosome / Type: RIBOSOME / Entity ID: #1-#82, #84 / Source: NATURAL |
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Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
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: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 44 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Details: Relion / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 105095 / Symmetry type: POINT |