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Open data
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Basic information
| Entry | Database: PDB / ID: 8k2c | ||||||
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| Title | Cryo-EM structure of the human 80S ribosome with Tigecycline | ||||||
Components |
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Keywords | RIBOSOME / Tigecycline / antibiotic | ||||||
| Function / homology | Function and homology informationribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV ...ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / axial mesoderm development / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / positive regulation of respiratory burst involved in inflammatory response / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / positive regulation of DNA-templated transcription initiation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / TNFR1-mediated ceramide production / alpha-beta T cell differentiation / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / negative regulation of RNA splicing / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / cytoplasmic translational initiation / NF-kappaB complex / negative regulation of DNA repair / G1 to G0 transition / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / ion channel inhibitor activity / protein kinase A binding / laminin receptor activity / Ribosomal scanning and start codon recognition / pigmentation / homeostatic process / positive regulation of mitochondrial depolarization / Translation initiation complex formation / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / Protein hydroxylation / monocyte chemotaxis / BH3 domain binding / negative regulation of translational frameshifting / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / SARS-CoV-1 modulates host translation machinery / positive regulation of GTPase activity / mTORC1-mediated signalling / TOR signaling / iron-sulfur cluster binding / Peptide chain elongation / regulation of cell division / cellular response to ethanol / Selenocysteine synthesis / Formation of a pool of free 40S subunits / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of protein binding / Eukaryotic Translation Termination / protein serine/threonine kinase inhibitor activity / blastocyst development / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / ubiquitin ligase inhibitor activity / negative regulation of respiratory burst involved in inflammatory response / Viral mRNA Translation / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / positive regulation of signal transduction by p53 class mediator / negative regulation of ubiquitin-dependent protein catabolic process / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.4 Å | ||||||
Authors | Li, X. / Wang, M. / 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 | 8k2c.cif.gz | 5 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8k2c.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8k2c.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k2/8k2c ftp://data.pdbj.org/pub/pdb/validation_reports/k2/8k2c | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 36838MC ![]() 8k2aC ![]() 8k2bC ![]() 8k2dC ![]() 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 F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-RNA chain , 5 types, 5 molecules L5L7L8S2CC
| #1: RNA chain | Mass: 1640182.000 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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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) |
| #3: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #49: RNA chain | Mass: 602752.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #85: RNA chain | Mass: 24231.510 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
+60S ribosomal protein ... , 42 types, 42 molecules LALBLCLDLELFLGLHLJLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLdLeLf...
-Large ribosomal subunit protein ... , 2 types, 2 molecules LILs
| #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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| #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 |
-Protein , 6 types, 6 molecules LmSgSfCACBCE
| #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 |
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| #70: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
| #82: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
| #83: Protein | Mass: 43851.879 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9UQ80 |
| #84: Protein | Mass: 45051.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q8NC51 |
| #86: Protein | Mass: 25890.377 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q96CT7 |
+40S ribosomal protein ... , 31 types, 31 molecules SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSe
-Non-polymers , 3 types, 276 molecules 




| #87: Chemical | ChemComp-MG / #88: Chemical | ChemComp-T1C / #89: Chemical | ChemComp-ZN / |
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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: 55S mitoribosome with tigecycline / Type: RIBOSOME / Entity ID: #1-#83 / 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 |
| 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 |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (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: 2.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 157229 / Symmetry type: POINT |
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Homo sapiens (human)
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FIELD EMISSION GUN