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- PDB-9g6j: The structure of the Candida albicans ribosome with tRNA-fMet, mR... -
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Open data
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Basic information
Entry | Database: PDB / ID: 9g6j | ||||||||||||||||||||||||
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Title | The structure of the Candida albicans ribosome with tRNA-fMet, mRNA, and compounds (GEN and MFQ) with strong density for the P-site tRNA | ||||||||||||||||||||||||
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![]() | RIBOSOME / Candida albicans / mRNA / mefloquine / geneticin G418 | ||||||||||||||||||||||||
Function / homology | ![]() filamentous growth of a population of unicellular organisms in response to neutral pH / cellular response to neutral pH / filamentous growth of a population of unicellular organisms in response to biotic stimulus / filamentous growth of a population of unicellular organisms in response to starvation / negative regulation of cell integrity MAPK cascade / positive regulation of conjugation with cellular fusion / yeast-form cell wall / fungal biofilm matrix / GCN2-mediated signaling / regulation of cytoplasmic translation ...filamentous growth of a population of unicellular organisms in response to neutral pH / cellular response to neutral pH / filamentous growth of a population of unicellular organisms in response to biotic stimulus / filamentous growth of a population of unicellular organisms in response to starvation / negative regulation of cell integrity MAPK cascade / positive regulation of conjugation with cellular fusion / yeast-form cell wall / fungal biofilm matrix / GCN2-mediated signaling / regulation of cytoplasmic translation / invasive growth in response to glucose limitation / hyphal cell wall / negative regulation of p38MAPK cascade / filamentous growth / negative regulation of glucose mediated signaling pathway / positive regulation of translational fidelity / ribosome-associated ubiquitin-dependent protein catabolic process / GDP-dissociation inhibitor activity / pre-mRNA 5'-splice site binding / preribosome, small subunit precursor / nonfunctional rRNA decay / mRNA destabilization / signaling receptor activator activity / negative regulation of translational frameshifting / negative regulation of mRNA splicing, via spliceosome / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / translational elongation / regulation of amino acid metabolic process / G-protein alpha-subunit binding / ribosomal subunit export from nucleus / 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) / protein-RNA complex assembly / maturation of LSU-rRNA / ribosomal small subunit export from nucleus / translation regulator activity / positive regulation of autophagy / rescue of stalled ribosome / DNA-(apurinic or apyrimidinic site) endonuclease activity / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / cellular response to starvation / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / protein kinase C binding / maturation of SSU-rRNA / small-subunit processome / maintenance of translational fidelity / modification-dependent protein catabolic process / protein tag activity / rRNA processing / extracellular vesicle / ribosome biogenesis / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / 5S rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / cell adhesion / negative regulation of translation / rRNA binding / protein ubiquitination / ribosome / structural constituent of ribosome / G protein-coupled receptor signaling pathway / translation / ribonucleoprotein complex / mRNA binding / ubiquitin protein ligase binding / nucleolus / cell surface / RNA binding / zinc ion binding / extracellular region / nucleus / metal ion binding / membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.15 Å | ||||||||||||||||||||||||
![]() | Kolosova, O. / Zgadzay, Y. / Jenner, L.B. / Guskov, A. / Yusupov, M. | ||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Mechanism of read-through enhancement by aminoglycosides and mefloquine. Authors: Olga Kolosova / Yury Zgadzay / Artem Stetsenko / Anastasia P Sukhinina / Anastasia Atamas / Shamil Validov / Andrey Rogachev / Konstantin Usachev / Lasse Jenner / Sergey E Dmitriev / Gulnara ...Authors: Olga Kolosova / Yury Zgadzay / Artem Stetsenko / Anastasia P Sukhinina / Anastasia Atamas / Shamil Validov / Andrey Rogachev / Konstantin Usachev / Lasse Jenner / Sergey E Dmitriev / Gulnara Yusupova / Albert Guskov / Marat Yusupov / ![]() ![]() ![]() Abstract: Nonsense mutations are associated with numerous and diverse pathologies, yet effective treatment strategies remain elusive. A promising approach to combat these conditions involves the use of ...Nonsense mutations are associated with numerous and diverse pathologies, yet effective treatment strategies remain elusive. A promising approach to combat these conditions involves the use of aminoglycosides, particularly in combination with stop-codon read-through enhancers, for developing drugs that can rescue the production of full-length proteins. Using X-ray crystallography and single-particle cryo-EM, we obtained structures of the eukaryotic ribosome in complexes with several aminoglycosides (geneticin G418, paromomycin, and hygromycin B) and the antimalarial drug mefloquine (MFQ), which has also been identified as a read-through enhancer. Our study reveals a binding site of MFQ, which holds significant promise for the development of therapies targeting premature termination codon-related genetic and oncological diseases. The results underscore the crucial role of the bridge B7b/c in mediating the effects of MFQ on subunit rotation dynamics. Through a comprehensive analysis of the interactions between the drugs and the eukaryotic ribosome, we propose a unifying hypothesis for read-through enhancement by small molecules, highlighting the role of decoding center rearrangements and intersubunit rotation dynamics. | ||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 4.3 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 3.4 MB | Display | ![]() |
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Full document | ![]() | 3.7 MB | Display | |
Data in XML | ![]() | 358.5 KB | Display | |
Data in CIF | ![]() | 616.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 51103MC ![]() 9g1zC ![]() 9g30C C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-60S ribosomal protein ... , 9 types, 9 molecules 0knptAAACAJAM
#1: Protein | Mass: 20376.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#45: Protein | Mass: 44040.848 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#48: Protein | Mass: 19798.002 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#50: Protein | Mass: 28549.424 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#54: Protein | Mass: 23105.771 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#61: Protein | Mass: 15551.407 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#63: Protein | Mass: 7135.336 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#70: Protein | Mass: 11096.161 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#73: Protein | Mass: 6347.549 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-RNA chain , 6 types, 7 molecules 134APTATMR
#2: RNA chain | Mass: 1085306.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
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#4: RNA chain | Mass: 38943.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#5: RNA chain | Mass: 50683.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#10: RNA chain | Mass: 575838.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#78: RNA chain | Mass: 24802.785 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #79: RNA chain | | Mass: 12383.539 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+Ribosomal 60S subunit protein ... , 26 types, 26 molecules 26789jlmoqrsuwxyABADAEAFAGAHAIALAPAQ
-40S ribosomal protein ... , 14 types, 14 molecules BCFHIJNWXZabcf
#11: Protein | Mass: 28759.307 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#12: Protein | Mass: 29041.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#15: Protein | Mass: 29435.354 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#17: Protein | Mass: 27146.469 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#18: Protein | Mass: 21285.818 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#19: Protein | Mass: 22801.979 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#23: Protein | Mass: 15715.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#32: Protein | Mass: 9652.814 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#33: Protein | Mass: 14807.189 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#35: Protein | Mass: 15546.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#36: Protein | Mass: 11633.762 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#37: Protein | Mass: 13606.099 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#38: Protein | Mass: 8982.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#41: Protein | Mass: 7127.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Ribosomal 40S subunit protein ... , 17 types, 17 molecules DEGKLMOPQTRSUVYde
#13: Protein | Mass: 26917.314 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#14: Protein | Mass: 27313.570 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#16: Protein | Mass: 25319.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#20: Protein | Mass: 21765.146 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#21: Protein | Mass: 13836.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#22: Protein | Mass: 17638.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#24: Protein | Mass: 16976.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#25: Protein | Mass: 14052.112 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#26: Protein | Mass: 15967.796 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#27: Protein | Mass: 17023.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#28: Protein | Mass: 15769.456 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#29: Protein | Mass: 15770.298 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#30: Protein | Mass: 16097.218 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#31: Protein | Mass: 13366.540 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#34: Protein | Mass: 16000.784 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#39: Protein | Mass: 7536.808 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#40: Protein | Mass: 6615.582 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 3 types, 3 molecules ghAN
#42: Protein | Mass: 22615.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#43: Protein | Mass: 34593.934 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#74: Protein | Mass: 6078.412 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Ribosomal protein ... , 3 types, 3 molecules vzAK
#56: Protein | Mass: 24389.256 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#60: Protein | Mass: 21942.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#71: Protein | Mass: 10102.830 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein/peptide , 1 types, 1 molecules AO
#75: Protein/peptide | Mass: 3396.280 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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-Non-polymers , 4 types, 25 molecules 






#80: Chemical | ChemComp-SPK / | ||||
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#81: Chemical | ChemComp-GET / #82: Chemical | ChemComp-ZN / #83: Chemical | ChemComp-YMZ / ( | |
-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-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: Candida albicans ribosome in complex with initiator fMet-tRNA, mRNA, and GEN+MFQ Type: RIBOSOME / Entity ID: #1-#79 / Source: NATURAL |
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Molecular weight | Value: 3.3 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.5 |
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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1200 nm / Nominal defocus min: 200 nm |
Image recording | Electron dose: 29.7 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
EM software | Name: PHENIX / Version: 1.19rc4_4035: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.15 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 63238 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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