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Yorodumi- PDB-8xsy: Cryo-EM structure of the human 80S ribosome with Tigecycline, e-t... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 8xsy | ||||||
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| Title | Cryo-EM structure of the human 80S ribosome with Tigecycline, e-tRNA and CCDC124 (40S head Swivelled) | ||||||
Components |
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Keywords | RIBOSOME / Tigecycline / antibiotic / CCDC124 | ||||||
| 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 / response to insecticide / eukaryotic 80S initiation complex / negative regulation of protein neddylation ...ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / translation at presynapse / exit from mitosis / response to insecticide / eukaryotic 80S initiation complex / negative regulation of protein neddylation / optic nerve development / regulation of translation involved in cellular response to UV / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / ribosomal protein import into nucleus / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein-DNA complex disassembly / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / 90S preribosome assembly / retinal ganglion cell axon guidance / protein tyrosine kinase inhibitor activity / nucleolus organization / positive regulation of endodeoxyribonuclease activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / alpha-beta T cell differentiation / G1 to G0 transition / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / middle ear morphogenesis / positive regulation of ubiquitin-protein transferase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / rRNA modification in the nucleus and cytosol / negative regulation of phagocytosis / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of ubiquitin protein ligase activity / laminin receptor activity / protein kinase A binding / homeostatic process / ion channel inhibitor activity / Ribosomal scanning and start codon recognition / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / macrophage chemotaxis / lung morphogenesis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / monocyte chemotaxis / negative regulation of translational frameshifting / TOR signaling / Protein hydroxylation / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / cellular response to ethanol / regulation of cell division / mTORC1-mediated signalling / Peptide chain elongation / Selenocysteine synthesis / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Formation of a pool of free 40S subunits / cellular response to actinomycin D / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Eukaryotic Translation Termination / blastocyst development / positive regulation of GTPase activity / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / Response of EIF2AK4 (GCN2) to amino acid deficiency / protein serine/threonine kinase inhibitor activity / ubiquitin ligase inhibitor activity / Viral mRNA Translation / positive regulation of signal transduction by p53 class mediator / negative regulation of respiratory burst involved in inflammatory response Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 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 | 8xsy.cif.gz | 4.9 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8xsy.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8xsy.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 8xsy_validation.pdf.gz | 2.6 MB | Display | wwPDB validaton report |
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| Full document | 8xsy_full_validation.pdf.gz | 2.7 MB | Display | |
| Data in XML | 8xsy_validation.xml.gz | 372.7 KB | Display | |
| Data in CIF | 8xsy_validation.cif.gz | 645.3 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xs/8xsy ftp://data.pdbj.org/pub/pdb/validation_reports/xs/8xsy | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 38630MC ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 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) / 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: 23899 |
| #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 |
| #49: 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 |
| #85: RNA chain | Mass: 24231.510 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 174924 |
+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, 271 molecules 




| #87: Chemical | ChemComp-MG / #88: Chemical | ChemComp-T1C / #89: 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 tigecycline, E-tRNA and CCDC124 / Type: RIBOSOME / Entity ID: #1-#86 / 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 mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
| 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: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
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| CTF correction | Details: Relion / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 46089 / 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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FIELD EMISSION GUN
