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Yorodumi- PDB-9g1z: Structure of Candida albicans 80S ribosome in complex with mefloq... -
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Basic information
| Entry | Database: PDB / ID: 9g1z | ||||||||||||||||||||||||
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| Title | Structure of Candida albicans 80S ribosome in complex with mefloquine (non-rotated state) | ||||||||||||||||||||||||
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Keywords | RIBOSOME / Candida Albicans / Readthrough / Mefloquine | ||||||||||||||||||||||||
| Function / homology | Function and homology informationfilamentous 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 starvation / filamentous growth of a population of unicellular organisms in response to biotic stimulus / negative regulation of cell integrity MAPK cascade / positive regulation of conjugation with cellular fusion / yeast-form cell wall / regulation of cytoplasmic translation / fungal biofilm matrix / invasive growth in response to glucose limitation ...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 starvation / filamentous growth of a population of unicellular organisms in response to biotic stimulus / negative regulation of cell integrity MAPK cascade / positive regulation of conjugation with cellular fusion / yeast-form cell wall / regulation of cytoplasmic translation / fungal biofilm matrix / invasive growth in response to glucose limitation / GCN2-mediated signaling / hyphal cell wall / preribosome / ribosome hibernation / negative regulation of p38MAPK cascade / filamentous growth / regulation of amino acid metabolic process / 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 / negative regulation of translational frameshifting / negative regulation of mRNA splicing, via spliceosome / signaling receptor activator activity / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / translational elongation / G-protein alpha-subunit binding / ribosomal subunit export from nucleus / protein-RNA complex assembly / 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) / maturation of LSU-rRNA / ribosomal small subunit export from nucleus / translation regulator activity / protein-membrane adaptor activity / DNA-(apurinic or apyrimidinic site) endonuclease activity / positive regulation of autophagy / rescue of stalled ribosome / protein kinase C binding / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / cellular response to starvation / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 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 / 5S rRNA binding / small ribosomal subunit 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 / structural constituent of ribosome / ribosome / translation / G protein-coupled receptor signaling pathway / ribonucleoprotein complex / mRNA binding / ubiquitin protein ligase binding / nucleolus / cell surface / RNA binding / extracellular region / zinc ion binding / nucleus / membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Candida albicans SC5314 (yeast) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||||||||||||||
Authors | Kolosova, O. / Zgadzay, Y. / Stetsenko, A. / Atamas, A. / Jenner, L.B. / Guskov, A. / Yusupov, M. | ||||||||||||||||||||||||
| Funding support | France, 3items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2025Title: 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. | ||||||||||||||||||||||||
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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 | 9g1z.cif.gz | 4.2 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb9g1z.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9g1z.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9g1z_validation.pdf.gz | 2.6 MB | Display | wwPDB validaton report |
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| Full document | 9g1z_full_validation.pdf.gz | 2.9 MB | Display | |
| Data in XML | 9g1z_validation.xml.gz | 367.8 KB | Display | |
| Data in CIF | 9g1z_validation.cif.gz | 612.1 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/g1/9g1z ftp://data.pdbj.org/pub/pdb/validation_reports/g1/9g1z | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 50957MC ![]() 9g30C ![]() 9g6jC 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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Assembly
| Deposited unit | ![]()
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Components
-60S ribosomal protein ... , 10 types, 10 molecules 0ktnpAAACAJAMAO
| #1: Protein | Mass: 20376.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PLC9 |
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| #45: Protein | Mass: 44040.848 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q59LS1 |
| #51: Protein | Mass: 23105.771 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: O59931 |
| #59: Protein | Mass: 19798.002 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PCX8 |
| #60: Protein | Mass: 28549.424 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5ANA1 |
| #63: Protein | Mass: 15551.407 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PFG4 |
| #65: Protein | Mass: 7135.336 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PF57 |
| #72: Protein | Mass: 11096.161 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PH21 |
| #75: Protein | Mass: 6347.549 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PDT4 |
| #77: Protein/peptide | Mass: 3396.280 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A2V1AQU0 |
+Ribosomal 60S subunit protein ... , 26 types, 26 molecules 256789jlmoqsuwyrxABADAEAFAGAIALAPAQ
-RNA chain , 5 types, 5 molecules 34A110
| #3: RNA chain | Mass: 38943.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: GenBank: 1111963231 |
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| #4: RNA chain | Mass: 50683.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: GenBank: 1817956650 |
| #10: RNA chain | Mass: 575838.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: GenBank: 1078736431 |
| #57: RNA chain | Mass: 1085306.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: GenBank: 1078736431 |
| #58: RNA chain | Mass: 24385.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) |
-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) Candida albicans SC5314 (yeast) / References: UniProt: O42817 |
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| #12: Protein | Mass: 29041.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: P40910 |
| #15: Protein | Mass: 29435.354 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PCI6 |
| #17: Protein | Mass: 27146.469 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PL99 |
| #18: Protein | Mass: 21285.818 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5AJ93 |
| #19: Protein | Mass: 22801.979 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q59T44 |
| #23: Protein | Mass: 15715.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5ADQ6 |
| #32: Protein | Mass: 9652.814 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PCG7 |
| #33: Protein | Mass: 14807.189 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q96W54 |
| #35: Protein | Mass: 15546.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5A7K0 |
| #36: Protein | Mass: 11633.762 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PNQ6 |
| #37: Protein | Mass: 13606.099 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5ALV6 |
| #38: Protein | Mass: 8982.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PTI7 |
| #41: Protein | Mass: 7127.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PSK2 |
-Ribosomal 40S subunit protein ... , 16 types, 16 molecules DEGKLMOQRSTUVYde
| #13: Protein | Mass: 26917.314 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5A900 |
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| #14: Protein | Mass: 27313.570 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PSV5 |
| #16: Protein | Mass: 25319.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5AG43 |
| #20: Protein | Mass: 21765.146 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PGY8 |
| #21: Protein | Mass: 13836.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PI15 |
| #22: Protein | Mass: 17638.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PN83 |
| #24: Protein | Mass: 16976.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PPE0 |
| #26: Protein | Mass: 15967.796 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PK22 |
| #27: Protein | Mass: 15769.456 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PCW6 |
| #28: Protein | Mass: 15770.298 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PEY9 |
| #29: Protein | Mass: 17023.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PQQ5 |
| #30: Protein | Mass: 16097.218 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PK61 |
| #31: Protein | Mass: 13366.540 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5A389 |
| #34: Protein | Mass: 16000.784 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PDU3 |
| #39: Protein | Mass: 7536.808 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PQN0 |
| #40: Protein | Mass: 6615.582 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PTR4 |
-Protein , 5 types, 5 molecules PghAHAN
| #25: Protein | Mass: 14052.112 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PDT3 |
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| #42: Protein | Mass: 22615.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5A109 |
| #43: Protein | Mass: 34593.934 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: P83774 |
| #70: Protein | Mass: 13645.102 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PDZ1 |
| #76: Protein | Mass: 6078.412 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PL68 |
-Ribosomal protein ... , 3 types, 3 molecules vzAK
| #53: Protein | Mass: 24389.256 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: Q5A6R1 |
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| #56: Protein | Mass: 21942.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PK40 |
| #73: Protein | Mass: 10102.830 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: UniProt: A0A1D8PF45 |
-Non-polymers , 3 types, 10 molecules 




| #80: Chemical | ChemComp-ZN / #81: Chemical | #82: Chemical | ChemComp-SPK / | |
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-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 80S ribosome in complex with mefloquine (non-rotated state) Type: RIBOSOME / Entity ID: #1-#79 / Source: NATURAL |
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| Molecular weight | Value: 3.3 MDa / Experimental value: NO |
| Source (natural) | Organism: Candida albicans SC5314 (yeast) |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TALOS ARCTICA |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 16000 nm / Nominal defocus min: 5000 nm / Cs: 2.7 mm |
| Image recording | Electron dose: 47.3 e/Å2 / Film or detector model: GATAN K2 SUMMIT (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: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 51014 / Symmetry type: POINT | ||||||||||||||||||||||||
| Atomic model building | Space: REAL | ||||||||||||||||||||||||
| Refine LS restraints |
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Candida albicans SC5314 (yeast)
France, 3items
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FIELD EMISSION GUN