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Yorodumi- PDB-8yoo: Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline -
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Open data
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Basic information
| Entry | Database: PDB / ID: 8yoo | ||||||
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| Title | Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline | ||||||
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Keywords | RIBOSOME / Tigecycline / antibiotic / eEF2 / SERBP1 | ||||||
| Function / homology | Function and homology informationembryonic brain development / translation at presynapse / PD-L1(CD274) glycosylation and translocation to plasma membrane / response to insecticide / alpha-beta T cell differentiation / exit from mitosis / optic nerve development / negative regulation of myoblast fusion / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex ...embryonic brain development / translation at presynapse / PD-L1(CD274) glycosylation and translocation to plasma membrane / response to insecticide / alpha-beta T cell differentiation / exit from mitosis / optic nerve development / negative regulation of myoblast fusion / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / ribosomal protein import into nucleus / regulation of G1 to G0 transition / axial mesoderm development / negative regulation of endoplasmic reticulum unfolded protein response / Enterobacterial factors antagonize host defense / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein-DNA complex disassembly / negative regulation of formation of translation preinitiation complex / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / 90S preribosome assembly / middle ear morphogenesis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / positive regulation of ubiquitin-protein transferase activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / positive regulation of DNA-templated transcription initiation / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / negative regulation of RNA splicing / TORC2 complex binding / Dengue Virus Genome Translation and Replication / G1 to G0 transition / neural crest cell differentiation / ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA / supercoiled DNA binding / Maturation of DENV proteins / negative regulation of DNA repair / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / NF-kappaB complex / mRNA Polyadenylation / cytoplasmic translational initiation / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / erythrocyte homeostasis / regulation of establishment of cell polarity / negative regulation of phagocytosis / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / blastocyst development / pigmentation / ion channel inhibitor activity / protein kinase A binding / homeostatic process / laminin receptor activity / Ribosomal scanning and start codon recognition / positive regulation of mitochondrial depolarization / lung morphogenesis / Translation initiation complex formation / macrophage chemotaxis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / Protein hydroxylation / BH3 domain binding / negative regulation of translational frameshifting / TOR signaling / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / monocyte chemotaxis / AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) / GSK3B-mediated proteasomal degradation of PD-L1(CD274) / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / iron-sulfur cluster binding / positive regulation of GTPase activity / SPOP-mediated proteasomal degradation of PD-L1(CD274) / cellular response to ethanol / Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide / Peptide chain elongation / Selenocysteine synthesis / negative regulation of protein binding / Formation of a pool of free 40S subunits / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Eukaryotic Translation Termination / protein serine/threonine kinase inhibitor activity / negative regulation of respiratory burst involved in inflammatory response / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2 Å | ||||||
Authors | Li, X. / Wang, M. / Denk, T. / Cheng, J. | ||||||
| Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2024Title: 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. | ||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8yoo.cif.gz | 4.7 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8yoo.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8yoo.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yo/8yoo ftp://data.pdbj.org/pub/pdb/validation_reports/yo/8yoo | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 39455MC ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yopC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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| 1 |
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Components
-RNA chain , 4 types, 4 molecules L5L7L8S2
| #1: RNA chain | Mass: 1640182.000 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 86475748 |
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| #2: RNA chain | Mass: 38998.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 23898 |
| #3: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 555853 |
| #48: RNA chain | Mass: 602752.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 36162 |
+60S ribosomal protein ... , 41 types, 41 molecules LALBLCLDLELFLGLHLJLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLdLeLf...
-Large ribosomal subunit protein ... , 3 types, 3 molecules LILmLs
| #12: Protein | Mass: 24630.061 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P27635 |
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| #41: Protein | Mass: 14771.411 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62987 |
| #46: Protein | Mass: 34309.418 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P05388 |
+40S ribosomal protein ... , 31 types, 31 molecules SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSe
-Protein , 2 types, 2 molecules SgSf
| #69: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
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| #81: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
-Non-polymers , 3 types, 271 molecules 




| #82: Chemical | ChemComp-MG / #83: Chemical | ChemComp-T1C / #84: Chemical | ChemComp-ZN / |
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-Details
| Has ligand of interest | Y |
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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: 80S ribosome with 100um tigecycline / Type: RIBOSOME / Entity ID: #1-#81 / Source: NATURAL |
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| Source (natural) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.4 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Grid material: COPPER / Grid type: Quantifoil R3/3 |
| 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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
| Specimen holder | Cryogen: NITROGEN |
| Image recording | Electron dose: 44 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
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| CTF correction | Details: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
| 3D reconstruction | Resolution: 2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 310531 / Symmetry type: POINT | |||||||||||||||||||||
| Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | |||||||||||||||||||||
| Atomic model building | PDB-ID: 6Z6M Accession code: 6Z6M / Source name: PDB / Type: experimental model |
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Homo sapiens (human)
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