[English] 日本語
Yorodumi- PDB-8yoo: Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline -
+
Open data
-
Basic information
| Entry | Database: PDB / ID: 8yoo | ||||||
|---|---|---|---|---|---|---|---|
| Title | Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline | ||||||
Components |
| ||||||
Keywords | RIBOSOME / Tigecycline / antibiotic / eEF2 / SERBP1 | ||||||
| Function / homology | Function and homology informationembryonic brain development / translation at presynapse / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / ribosomal protein import into nucleus / negative regulation of endoplasmic reticulum unfolded protein response / regulation of G1 to G0 transition / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / oxidized pyrimidine DNA binding ...embryonic brain development / translation at presynapse / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / ribosomal protein import into nucleus / negative regulation of endoplasmic reticulum unfolded protein response / regulation of G1 to G0 transition / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / G1 to G0 transition / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of formation of translation preinitiation complex / positive regulation of ubiquitin-protein transferase activity / GAIT complex / nucleolus organization / positive regulation of DNA-templated transcription initiation / negative regulation of RNA splicing / negative regulation of DNA repair / TORC2 complex binding / positive regulation of DNA damage response, signal transduction by p53 class mediator / erythrocyte homeostasis / supercoiled DNA binding / regulation of establishment of cell polarity / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / NF-kappaB complex / cytoplasmic translational initiation / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / 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 / laminin receptor activity / negative regulation of myoblast fusion / ion channel inhibitor activity / positive regulation of mitochondrial depolarization / protein kinase A binding / Ribosomal scanning and start codon recognition / Translation initiation complex formation / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / Protein hydroxylation / TOR signaling / BH3 domain binding / negative regulation of translational frameshifting / monocyte chemotaxis / iron-sulfur cluster binding / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / gastrulation / protein localization to nucleus / positive regulation of GTPase activity / Peptide chain elongation / cellular response to ethanol / protein targeting / Selenocysteine synthesis / Formation of a pool of free 40S subunits / negative regulation of protein binding / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of respiratory burst involved in inflammatory response / protein serine/threonine kinase inhibitor activity / Eukaryotic Translation Termination / Dengue Virus Attachment and Entry / negative regulation of ubiquitin-dependent protein catabolic process / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / ubiquitin ligase inhibitor activity / 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 / GTP hydrolysis and joining of the 60S ribosomal subunit / embryo implantation / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / spindle assembly / positive regulation of microtubule polymerization / phagocytic cup / maturation of LSU-rRNA / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / protein-RNA complex assembly / positive regulation of intrinsic apoptotic signaling pathway / Protein methylation / 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) 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
| ||||||
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. | ||||||
| History |
|
-
Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
|---|
-
Downloads & links
-
Download
| PDBx/mmCIF format | 8yoo.cif.gz | 4.7 MB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| 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 |
|---|
-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 ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
-
Assembly
| Deposited unit | ![]()
|
|---|---|
| 1 |
|
-
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 |
|---|---|
| #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 |
|---|---|
| #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 |
|---|---|
| #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 / |
|---|
-Details
| Has ligand of interest | Y |
|---|
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
| Component | Name: 80S ribosome with 100um tigecycline / Type: RIBOSOME / Entity ID: #1-#81 / Source: NATURAL |
|---|---|
| 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 |
-
Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
|---|---|
| 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) |
-
Processing
| EM software |
| |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
Movie
Controller
About Yorodumi



Homo sapiens (human)
Citation
































PDBj























































FIELD EMISSION GUN
