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Yorodumi- EMDB-4434: Large subunit of the human mitochondrial ribosome in complex with... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4434 | |||||||||
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Title | Large subunit of the human mitochondrial ribosome in complex with Virginiamycin M and Quinupristin | |||||||||
Map data | Postprocessed, Sharpened Map | |||||||||
Sample |
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Keywords | Ribosome / Mitochondria | |||||||||
Function / homology | Function and homology information mitochondrial translational termination / mitochondrial translational elongation / translation release factor activity, codon nonspecific / microprocessor complex / Mitochondrial translation elongation / Mitochondrial translation termination / Mitochondrial translation initiation / mitochondrial large ribosomal subunit / peptidyl-tRNA hydrolase / mitochondrial ribosome ...mitochondrial translational termination / mitochondrial translational elongation / translation release factor activity, codon nonspecific / microprocessor complex / Mitochondrial translation elongation / Mitochondrial translation termination / Mitochondrial translation initiation / mitochondrial large ribosomal subunit / peptidyl-tRNA hydrolase / mitochondrial ribosome / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / mitochondrial small ribosomal subunit / mitochondrial translation / aminoacyl-tRNA hydrolase activity / anatomical structure morphogenesis / RNA processing / Mitochondrial protein degradation / rescue of stalled ribosome / cellular response to leukemia inhibitory factor / fibrillar center / double-stranded RNA binding / small ribosomal subunit rRNA binding / large ribosomal subunit / cell junction / large ribosomal subunit rRNA binding / 5S rRNA binding / endonuclease activity / mitochondrial inner membrane / negative regulation of translation / nuclear body / rRNA binding / ribosome / structural constituent of ribosome / mitochondrial matrix / translation / ribonucleoprotein complex / protein domain specific binding / mRNA binding / nucleotide binding / synapse / nucleolus / apoptotic process / mitochondrion / RNA binding / nucleoplasm / nucleus / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Modelska A / Aibara S | |||||||||
Funding support | Sweden, 1 items
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Citation | Journal: Cell Rep / Year: 2021 Title: Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth. Authors: Denise Sighel / Michela Notarangelo / Shintaro Aibara / Angela Re / Gianluca Ricci / Marianna Guida / Alessia Soldano / Valentina Adami / Chiara Ambrosini / Francesca Broso / Emanuele ...Authors: Denise Sighel / Michela Notarangelo / Shintaro Aibara / Angela Re / Gianluca Ricci / Marianna Guida / Alessia Soldano / Valentina Adami / Chiara Ambrosini / Francesca Broso / Emanuele Filiberto Rosatti / Sara Longhi / Mariachiara Buccarelli / Quintino G D'Alessandris / Stefano Giannetti / Simone Pacioni / Lucia Ricci-Vitiani / Joanna Rorbach / Roberto Pallini / Sandrine Roulland / Alexey Amunts / Ines Mancini / Angelika Modelska / Alessandro Quattrone / Abstract: Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore ...Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes. We identify the bacterial antibiotic quinupristin/dalfopristin (Q/D) as an effective suppressor of GSC growth. Q/D also decreases the clonogenicity of GSCs in vitro, consequently dysregulating the cell cycle and inducing apoptosis. Cryoelectron microscopy (cryo-EM) reveals that Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and functionally dysregulating OXPHOS complexes. These data suggest that targeting mitochondrial translation could be explored to therapeutically suppress GSC growth in GBM and that Q/D could potentially be repurposed for cancer treatment. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4434.map.gz | 36.9 MB | EMDB map data format | |
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Header (meta data) | emd-4434-v30.xml emd-4434.xml | 71.5 KB 71.5 KB | Display Display | EMDB header |
Images | emd_4434.png | 253.2 KB | ||
Masks | emd_4434_msk_1.map | 476.8 MB | Mask map | |
Filedesc metadata | emd-4434.cif.gz | 16 KB | ||
Others | emd_4434_half_map_1.map.gz emd_4434_half_map_2.map.gz | 382.5 MB 382.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4434 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4434 | HTTPS FTP |
-Validation report
Summary document | emd_4434_validation.pdf.gz | 857.5 KB | Display | EMDB validaton report |
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Full document | emd_4434_full_validation.pdf.gz | 857.1 KB | Display | |
Data in XML | emd_4434_validation.xml.gz | 18.1 KB | Display | |
Data in CIF | emd_4434_validation.cif.gz | 21.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4434 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4434 | HTTPS FTP |
-Related structure data
Related structure data | 6i9rMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4434.map.gz / Format: CCP4 / Size: 476.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Postprocessed, Sharpened Map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_4434_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half Map A
File | emd_4434_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_4434_half_map_2.map | ||||||||||||
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Annotation | Half Map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Large subunit of the human mitochondrial ribosome in complex with...
+Supramolecule #1: Large subunit of the human mitochondrial ribosome in complex with...
+Macromolecule #1: 39S ribosomal protein L32, mitochondrial
+Macromolecule #2: 39S ribosomal protein L33, mitochondrial
+Macromolecule #3: 39S ribosomal protein L34, mitochondrial
+Macromolecule #4: 39S ribosomal protein L35, mitochondrial
+Macromolecule #5: 39S ribosomal protein L36, mitochondrial
+Macromolecule #6: 39S ribosomal protein L37, mitochondrial
+Macromolecule #7: 39S ribosomal protein L38, mitochondrial
+Macromolecule #8: 39S ribosomal protein L39, mitochondrial
+Macromolecule #9: 39S ribosomal protein L40, mitochondrial
+Macromolecule #10: 39S ribosomal protein L41, mitochondrial
+Macromolecule #13: 39S ribosomal protein L2, mitochondrial
+Macromolecule #14: 39S ribosomal protein L3, mitochondrial
+Macromolecule #15: 39S ribosomal protein L4, mitochondrial
+Macromolecule #16: 39S ribosomal protein L9, mitochondrial
+Macromolecule #17: 39S ribosomal protein L10, mitochondrial
+Macromolecule #18: 39S ribosomal protein L11, mitochondrial
+Macromolecule #19: 39S ribosomal protein L13, mitochondrial
+Macromolecule #20: 39S ribosomal protein L14, mitochondrial
+Macromolecule #21: 39S ribosomal protein L15, mitochondrial
+Macromolecule #22: 39S ribosomal protein L16, mitochondrial
+Macromolecule #23: 39S ribosomal protein L17, mitochondrial
+Macromolecule #24: Mitochondrial ribosomal protein L18, isoform CRA_b
+Macromolecule #25: 39S ribosomal protein L19, mitochondrial
+Macromolecule #26: 39S ribosomal protein L20, mitochondrial
+Macromolecule #27: 39S ribosomal protein L21, mitochondrial
+Macromolecule #28: 39S ribosomal protein L22, mitochondrial
+Macromolecule #29: 39S ribosomal protein L23, mitochondrial
+Macromolecule #30: 39S ribosomal protein L24, mitochondrial
+Macromolecule #31: 39S ribosomal protein L27, mitochondrial
+Macromolecule #32: 39S ribosomal protein L28, mitochondrial
+Macromolecule #33: 39S ribosomal protein L47, mitochondrial
+Macromolecule #34: 39S ribosomal protein L30, mitochondrial
+Macromolecule #35: 39S ribosomal protein L42, mitochondrial
+Macromolecule #36: 39S ribosomal protein L43, mitochondrial
+Macromolecule #37: 39S ribosomal protein L44, mitochondrial
+Macromolecule #38: 39S ribosomal protein L45, mitochondrial
+Macromolecule #39: 39S ribosomal protein L46, mitochondrial
+Macromolecule #40: 39S ribosomal protein L48, mitochondrial
+Macromolecule #41: 39S ribosomal protein L49, mitochondrial
+Macromolecule #42: 39S ribosomal protein L50, mitochondrial
+Macromolecule #43: 39S ribosomal protein L51, mitochondrial
+Macromolecule #44: cDNA FLJ76418, highly similar to Homo sapiens mitochondrial ribos...
+Macromolecule #45: 39S ribosomal protein L53, mitochondrial
+Macromolecule #46: 39S ribosomal protein L54, mitochondrial
+Macromolecule #47: 39S ribosomal protein L55, mitochondrial
+Macromolecule #48: Ribosomal protein 63, mitochondrial
+Macromolecule #49: Peptidyl-tRNA hydrolase ICT1, mitochondrial
+Macromolecule #50: Growth arrest and DNA damage-inducible proteins-interacting protein 1
+Macromolecule #51: 39S ribosomal protein S18a, mitochondrial
+Macromolecule #52: 39S ribosomal protein S30, mitochondrial
+Macromolecule #53: Quinupristin
+Macromolecule #11: 16S rRNA
+Macromolecule #12: tRNA Val
+Macromolecule #54: ZINC ION
+Macromolecule #55: MAGNESIUM ION
+Macromolecule #56: GUANOSINE-5'-MONOPHOSPHATE
+Macromolecule #57: Virginiamycin M
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 38.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 100000 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-6i9r: |