+
Open data
-
Basic information
| Entry | Database: PDB / ID: 8k2a | ||||||
|---|---|---|---|---|---|---|---|
| Title | Cryo-EM structure of the human 55S mitoribosome with Tigecycline | ||||||
Components |
| ||||||
Keywords | RIBOSOME / 55S mitoribosome / Tigecycline / antibiotic | ||||||
| Function / homology | Function and homology informationmitochondrial translational termination / mitochondrial ribosome assembly / mitochondrial translational elongation / Mitochondrial translation elongation / Mitochondrial translation termination / translation release factor activity, codon nonspecific / Mitochondrial translation initiation / translation release factor activity / negative regulation of mitotic nuclear division / mitochondrial large ribosomal subunit ...mitochondrial translational termination / mitochondrial ribosome assembly / mitochondrial translational elongation / Mitochondrial translation elongation / Mitochondrial translation termination / translation release factor activity, codon nonspecific / Mitochondrial translation initiation / translation release factor activity / negative regulation of mitotic nuclear division / mitochondrial large ribosomal subunit / peptidyl-tRNA hydrolase / mitochondrial ribosome / mitochondrial small ribosomal subunit / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / peptidyl-tRNA hydrolase activity / mitochondrial translation / apoptotic mitochondrial changes / positive regulation of proteolysis / ribosomal small subunit binding / anatomical structure morphogenesis / RNA processing / Mitochondrial protein degradation / rescue of stalled ribosome / cellular response to leukemia inhibitory factor / apoptotic signaling pathway / fibrillar center / cell junction / large ribosomal subunit / double-stranded RNA binding / regulation of translation / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / large ribosomal subunit rRNA binding / endonuclease activity / nuclear membrane / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / tRNA binding / cell population proliferation / mitochondrial inner membrane / negative regulation of translation / rRNA binding / nuclear body / structural constituent of ribosome / ribosome / translation / mitochondrial matrix / ribonucleoprotein complex / protein domain specific binding / nucleotide binding / intracellular membrane-bounded organelle / mRNA binding / apoptotic process / GTP binding / nucleolus / mitochondrion / RNA binding / nucleoplasm / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||
Authors | Li, X. / Wang, M. / 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 | 8k2a.cif.gz | 4.1 MB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| PDB format | pdb8k2a.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8k2a.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 8k2a_validation.pdf.gz | 2 MB | Display | wwPDB validaton report |
|---|---|---|---|---|
| Full document | 8k2a_full_validation.pdf.gz | 2.2 MB | Display | |
| Data in XML | 8k2a_validation.xml.gz | 335.1 KB | Display | |
| Data in CIF | 8k2a_validation.cif.gz | 583.7 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k2/8k2a ftp://data.pdbj.org/pub/pdb/validation_reports/k2/8k2a | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 36836MC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yooC ![]() 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 , 3 types, 3 molecules L1L2S1
| #1: RNA chain | Mass: 500019.594 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
|---|---|
| #2: RNA chain | Mass: 22022.131 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #83: RNA chain | Mass: 306135.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
+Large ribosomal subunit protein ... , 47 types, 47 molecules LBLCLDLILJLKLMLNLOLPLQLSLTLULWLXLaLbLuLdLfLgLhLiLjLkLlLmLnLo...
-Protein , 1 types, 1 molecules LR
| #14: Protein | Mass: 20465.348 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A8K9D2 |
|---|
-39S ribosomal protein ... , 2 types, 2 molecules LVLz
| #18: Protein | Mass: 24369.527 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: E7ESL0 |
|---|---|
| #44: Protein | Mass: 13696.684 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A8K7J6 |
+Small ribosomal subunit protein ... , 30 types, 30 molecules SBSZSESFSGSISJSKSLSNSOSPSQSSSTSWSXSYSaSbScSdSeSgSiSjSkSmSnSo
-Non-polymers , 4 types, 157 molecules 






| #84: Chemical | ChemComp-MG / #85: Chemical | ChemComp-T1C / #86: Chemical | ChemComp-ZN / #87: Chemical | ChemComp-GDP / | |
|---|
-Details
| Has protein modification | Y |
|---|
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
| Component | Name: 55S mitoribosome with tigecycline / Type: RIBOSOME / Entity ID: #1-#83 / 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 |
| 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 |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-
Processing
| CTF correction | Details: Relion / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
|---|---|
| 3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 143725 / Symmetry type: POINT |
Movie
Controller
About Yorodumi




Homo sapiens (human)
Citation
































PDBj







































FIELD EMISSION GUN