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Yorodumi- EMDB-50990: Cryo-EM map of the Candida albicans ribosome with tRNA-fMet, mRNA... -
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Basic information
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| Title | Cryo-EM map of the Candida albicans ribosome with tRNA-fMet, mRNA, and compounds (GEN and MFQ) shows strong density for the A site tRNA | ||||||||||||
Map data | Cryo-EM map of the Candida albicans ribosome in complex with mRNA and initiator tRNA (strong A site tRNA), and two compounds. | ||||||||||||
Sample |
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Keywords | Candida albicans / ribosome / mRNA / mefloquine / geneticin G418 | ||||||||||||
| 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 / invasive growth in response to glucose limitation / GCN2-mediated signaling ...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 / 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 / nonfunctional rRNA decay / preribosome, small subunit precursor / mRNA destabilization / negative regulation of translational frameshifting / negative regulation of mRNA splicing, via spliceosome / signaling receptor activator activity / translational elongation / G-protein alpha-subunit binding / 90S preribosome / ribosomal subunit export from nucleus / protein-RNA complex assembly / 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 / large ribosomal subunit / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / ribosomal large subunit assembly / small ribosomal subunit rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / 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 / metal ion binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||||||||
| Biological species | Candida albicans SC5314 (yeast) / Candida albicans (yeast) | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.35 Å | ||||||||||||
Authors | Kolosova O / Zgadzay Y / Jenner LB / Guskov A / Yusupov M | ||||||||||||
| Funding support | France, 3 items
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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
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_50990.map.gz | 1.2 GB | EMDB map data format | |
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| Header (meta data) | emd-50990-v30.xml emd-50990.xml | 101.5 KB 101.5 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_50990_fsc.xml | 23 KB | Display | FSC data file |
| Images | emd_50990.png | 121.8 KB | ||
| Filedesc metadata | emd-50990.cif.gz | 19.5 KB | ||
| Others | emd_50990_half_map_1.map.gz emd_50990_half_map_2.map.gz | 1.2 GB 1.2 GB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-50990 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-50990 | HTTPS FTP |
-Validation report
| Summary document | emd_50990_validation.pdf.gz | 1.3 MB | Display | EMDB validaton report |
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| Full document | emd_50990_full_validation.pdf.gz | 1.3 MB | Display | |
| Data in XML | emd_50990_validation.xml.gz | 32.7 KB | Display | |
| Data in CIF | emd_50990_validation.cif.gz | 43.4 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-50990 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-50990 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9g30MC ![]() 9g1zC ![]() 9g6jC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_50990.map.gz / Format: CCP4 / Size: 1.3 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | Cryo-EM map of the Candida albicans ribosome in complex with mRNA and initiator tRNA (strong A site tRNA), and two compounds. | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.729 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: Half map A
| File | emd_50990_half_map_1.map | ||||||||||||
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| Annotation | Half map A | ||||||||||||
| Projections & Slices |
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| Density Histograms |
-Half map: Half map B
| File | emd_50990_half_map_2.map | ||||||||||||
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| Annotation | Half map B | ||||||||||||
| Projections & Slices |
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| Density Histograms |
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Sample components
+Entire : Candida albicans ribosome in complex with initiator fMet-tRNA, mR...
+Supramolecule #1: Candida albicans ribosome in complex with initiator fMet-tRNA, mR...
+Macromolecule #1: 60S ribosomal protein L20
+Macromolecule #3: 60S ribosomal protein L21-A
+Macromolecule #6: 60S ribosomal protein L23-A
+Macromolecule #7: 60S ribosomal protein L24-A
+Macromolecule #8: 60S ribosomal protein L25
+Macromolecule #9: Ribosomal protein L24
+Macromolecule #11: 40S ribosomal protein S0
+Macromolecule #12: 40S ribosomal protein S1
+Macromolecule #13: Ribosomal protein S5
+Macromolecule #14: Ribosomal protein S3
+Macromolecule #15: 40S ribosomal protein S4
+Macromolecule #16: Ribosomal protein S7
+Macromolecule #17: 40S ribosomal protein S6
+Macromolecule #18: 40S ribosomal protein S7
+Macromolecule #19: 40S ribosomal protein S8
+Macromolecule #20: Ribosomal protein S4
+Macromolecule #21: 40S ribosomal protein S10-A
+Macromolecule #22: 40S ribosomal protein S11A
+Macromolecule #23: 40S ribosomal protein S12
+Macromolecule #24: 40S ribosomal protein S13
+Macromolecule #25: 40S ribosomal protein S14-A
+Macromolecule #26: 40S ribosomal protein S15
+Macromolecule #27: 40S ribosomal protein S18-B
+Macromolecule #28: 40S ribosomal protein S16
+Macromolecule #29: 40S ribosomal protein S17-B
+Macromolecule #30: 40S ribosomal protein S19-A
+Macromolecule #31: Ribosomal protein S10
+Macromolecule #32: 40S ribosomal protein S21
+Macromolecule #33: 40S ribosomal protein S22-A
+Macromolecule #34: Ribosomal protein S23 (S12)
+Macromolecule #35: 40S ribosomal protein S24
+Macromolecule #36: 40S ribosomal protein S25
+Macromolecule #37: 40S ribosomal protein S26
+Macromolecule #38: 40S ribosomal protein S27
+Macromolecule #39: 40S ribosomal protein S28-B
+Macromolecule #40: 40S ribosomal protein S29A
+Macromolecule #41: 40S ribosomal protein S30
+Macromolecule #42: Ubiquitin-40S ribosomal protein S31 fusion protein
+Macromolecule #43: Guanine nucleotide-binding protein subunit beta-like protein
+Macromolecule #44: 60S ribosomal protein L2-B
+Macromolecule #45: 60S ribosomal protein L3
+Macromolecule #46: 60S ribosomal protein L4-B
+Macromolecule #47: 60S ribosomal protein L5
+Macromolecule #48: 60S ribosomal protein L6
+Macromolecule #49: 60S ribosomal protein L7-A
+Macromolecule #50: 60S ribosomal protein L8
+Macromolecule #51: 60S ribosomal protein L9-B
+Macromolecule #52: 60S ribosomal protein L10
+Macromolecule #53: 60S ribosomal protein L11-B
+Macromolecule #54: 60S ribosomal protein L13
+Macromolecule #55: 60S ribosomal protein L14-B
+Macromolecule #56: 60S ribosomal protein L15-A
+Macromolecule #57: Ribosomal protein L13
+Macromolecule #58: Ribosomal protein L22
+Macromolecule #59: 60S ribosomal protein L18-A
+Macromolecule #60: 60S ribosomal protein L19-A
+Macromolecule #61: 60S ribosomal protein L27
+Macromolecule #62: 60S ribosomal protein L28
+Macromolecule #63: 60S ribosomal protein L29
+Macromolecule #64: 60S ribosomal protein L30
+Macromolecule #65: 60S ribosomal protein L31-B
+Macromolecule #66: 60S ribosomal protein L32
+Macromolecule #67: 60S ribosomal protein L33-A
+Macromolecule #68: 60S ribosomal protein L34-B
+Macromolecule #69: Ribosomal protein L29
+Macromolecule #70: 60S ribosomal protein L36
+Macromolecule #71: 60S ribosomal protein L37-B
+Macromolecule #72: 60S ribosomal protein L38
+Macromolecule #73: 60S ribosomal protein L39
+Macromolecule #74: 60S ribosomal protein L40-B
+Macromolecule #75: 60S ribosomal protein L41
+Macromolecule #76: 60S ribosomal protein L42-B
+Macromolecule #77: 60S ribosomal protein L43-A
+Macromolecule #2: 25S rRNA
+Macromolecule #4: 5S rRNA
+Macromolecule #5: 5.8S rRNA
+Macromolecule #10: 18S rRNA
+Macromolecule #78: tRNA
+Macromolecule #79: mRNA
+Macromolecule #80: SPERMINE (FULLY PROTONATED FORM)
+Macromolecule #81: GENETICIN
+Macromolecule #82: ZINC ION
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 29.7 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.2 µm / Nominal defocus min: 0.2 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



Keywords
Candida albicans SC5314 (yeast)
Authors
France, 3 items
Citation













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Processing
FIELD EMISSION GUN


