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Yorodumi- EMDB-26034: Yeast 80S ribosome bound with the ALS/FTD-associated dipeptide re... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26034 | |||||||||||||||
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Title | Yeast 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein PR20 | |||||||||||||||
Map data | Yeast 80S ribosome with heterogeneous 40S and PR20 bound to the peptide tunnel | |||||||||||||||
Sample |
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Keywords | Ribosomal binding peptide / ALS/FTD-associated dipeptide repeat protein / RIBOSOME | |||||||||||||||
Function / homology | Function and homology information hexon binding / pre-mRNA 5'-splice site binding / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / SRP-dependent cotranslational protein targeting to membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Formation of a pool of free 40S subunits / negative regulation of mRNA splicing, via spliceosome ...hexon binding / pre-mRNA 5'-splice site binding / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / SRP-dependent cotranslational protein targeting to membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Formation of a pool of free 40S subunits / negative regulation of mRNA splicing, via spliceosome / preribosome, large subunit precursor / L13a-mediated translational silencing of Ceruloplasmin expression / ribosomal large subunit export from nucleus / 90S preribosome / regulation of translational fidelity / protein-RNA complex assembly / maturation of LSU-rRNA / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / macroautophagy / maintenance of translational fidelity / modification-dependent protein catabolic process / protein tag activity / rRNA processing / ribosome biogenesis / viral capsid / 5S rRNA binding / large ribosomal subunit rRNA binding / ribosomal large subunit assembly / cytoplasmic translation / cytosolic large ribosomal subunit / negative regulation of translation / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / translation / response to antibiotic / mRNA binding / ubiquitin protein ligase binding / host cell nucleus / nucleolus / RNA binding / nucleus / metal ion binding / cytosol / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Saccharomyces cerevisiae (brewer's yeast) / Escherichia coli (E. coli) / Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.4 Å | |||||||||||||||
Authors | Loveland AB / Svidritskiy E / Susorov D / Lee S / Park A / Zvornicanin S / Demo G / Gao FB / Korostelev AA | |||||||||||||||
Funding support | United States, 4 items
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Citation | Journal: Nat Commun / Year: 2022 Title: Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM. Authors: Anna B Loveland / Egor Svidritskiy / Denis Susorov / Soojin Lee / Alexander Park / Sarah Zvornicanin / Gabriel Demo / Fen-Biao Gao / Andrei A Korostelev / Abstract: Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ...Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two DPR proteins, poly-PR and poly-GR, repress cellular translation but the molecular mechanism remains unknown. Here we show that poly-PR and poly-GR of ≥20 repeats inhibit the ribosome's peptidyl-transferase activity at nanomolar concentrations, comparable to specific translation inhibitors. High-resolution cryogenic electron microscopy (cryo-EM) reveals that poly-PR and poly-GR block the polypeptide tunnel of the ribosome, extending into the peptidyl-transferase center (PTC). Consistent with these findings, the macrolide erythromycin, which binds in the tunnel, competes with poly-PR and restores peptidyl-transferase activity. Our results demonstrate that strong and specific binding of poly-PR and poly-GR in the ribosomal tunnel blocks translation, revealing the structural basis of their toxicity in C9ORF72-ALS/FTD. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26034.map.gz | 200.3 MB | EMDB map data format | |
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Header (meta data) | emd-26034-v30.xml emd-26034.xml | 67.7 KB 67.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26034_fsc.xml | 13.1 KB | Display | FSC data file |
Images | emd_26034.png | 36.6 KB | ||
Filedesc metadata | emd-26034.cif.gz | 13.2 KB | ||
Others | emd_26034_additional_1.map.gz emd_26034_half_map_1.map.gz emd_26034_half_map_2.map.gz | 200.6 MB 81.9 MB 81.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26034 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26034 | HTTPS FTP |
-Validation report
Summary document | emd_26034_validation.pdf.gz | 959.7 KB | Display | EMDB validaton report |
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Full document | emd_26034_full_validation.pdf.gz | 959.3 KB | Display | |
Data in XML | emd_26034_validation.xml.gz | 21.6 KB | Display | |
Data in CIF | emd_26034_validation.cif.gz | 28 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26034 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26034 | HTTPS FTP |
-Related structure data
Related structure data | 7topMC 7tooC 7toqC 7torC 7tosC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26034.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Yeast 80S ribosome with heterogeneous 40S and PR20 bound to the peptide tunnel | ||||||||||||||||||||||||||||||||||||
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:
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-Supplemental data
-Additional map: Map used for refinement, B-factor (-25) applied
File | emd_26034_additional_1.map | ||||||||||||
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Annotation | Map used for refinement, B-factor (-25) applied | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2
File | emd_26034_half_map_1.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1
File | emd_26034_half_map_2.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Yeast 80S ribosome bound with the ALS/FTD-associated dipeptide re...
+Supramolecule #1: Yeast 80S ribosome bound with the ALS/FTD-associated dipeptide re...
+Macromolecule #1: 25S rRNA
+Macromolecule #2: 5.8S rRNA
+Macromolecule #3: 5S rRNA
+Macromolecule #47: tRNAfMet
+Macromolecule #4: 60S ribosomal protein L2-A
+Macromolecule #5: RPL3 isoform 1
+Macromolecule #6: RPL4A isoform 1
+Macromolecule #7: RPL5 isoform 1
+Macromolecule #8: 60S ribosomal protein L6-A
+Macromolecule #9: 60S ribosomal protein L7-A
+Macromolecule #10: 60S ribosomal protein L8-A
+Macromolecule #11: 60S ribosomal protein L9-A
+Macromolecule #12: RPL10 isoform 1
+Macromolecule #13: RPL11A isoform 1
+Macromolecule #14: Ribosomal protein L12
+Macromolecule #15: 60S ribosomal protein L13-A
+Macromolecule #16: 60S ribosomal protein L14-A
+Macromolecule #17: 60S ribosomal protein L15-A
+Macromolecule #18: 60S ribosomal protein L16-A
+Macromolecule #19: 60S ribosomal protein L17-A
+Macromolecule #20: 60S ribosomal protein L18-A
+Macromolecule #21: 60S ribosomal protein L19-A
+Macromolecule #22: 60S ribosomal protein L20-A
+Macromolecule #23: 60S ribosomal protein L21-A
+Macromolecule #24: 60S ribosomal protein L22-A
+Macromolecule #25: 60S ribosomal protein L23-A
+Macromolecule #26: RPL24A isoform 1
+Macromolecule #27: 60S ribosomal protein L25
+Macromolecule #28: 60S ribosomal protein L26-A
+Macromolecule #29: 60S ribosomal protein L27-A
+Macromolecule #30: 60S ribosomal protein L28
+Macromolecule #31: RPL29 isoform 1
+Macromolecule #32: 60S ribosomal protein L30
+Macromolecule #33: 60S ribosomal protein L31-A
+Macromolecule #34: RPL32 isoform 1
+Macromolecule #35: 60S ribosomal protein L33-A
+Macromolecule #36: 60S ribosomal protein L34-A
+Macromolecule #37: 60S ribosomal protein L35-A
+Macromolecule #38: 60S ribosomal protein L36-A
+Macromolecule #39: 60S ribosomal protein L37-A
+Macromolecule #40: RPL38 isoform 1
+Macromolecule #41: 60S ribosomal protein L39
+Macromolecule #42: Ubiquitin-60S ribosomal protein L40
+Macromolecule #43: 60S ribosomal protein L41-A
+Macromolecule #44: 60S ribosomal protein L42-A
+Macromolecule #45: 60S ribosomal protein L43-A
+Macromolecule #46: 60S acidic ribosomal protein P0
+Macromolecule #48: PR20
+Macromolecule #49: ZINC ION
-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 / Chamber humidity: 95 % |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 30.0 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: 1.8 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |