[English] 日本語
Yorodumi- EMDB-26036: Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptid... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26036 | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein GR20 | |||||||||||||||
Map data | Rabbit 80S ribosome with GR20 | |||||||||||||||
Sample |
| |||||||||||||||
Function / homology | Function and homology information regulation of G1 to G0 transition / exit from mitosis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / mammalian oogenesis stage / retinal ganglion cell axon guidance / G1 to G0 transition ...regulation of G1 to G0 transition / exit from mitosis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / mammalian oogenesis stage / retinal ganglion cell axon guidance / G1 to G0 transition / activation-induced cell death of T cells / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / TOR signaling / T cell proliferation involved in immune response / ribosomal small subunit export from nucleus / erythrocyte development / translation regulator activity / cellular response to actinomycin D / cytosolic ribosome / rough endoplasmic reticulum / 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) / gastrulation / MDM2/MDM4 family protein binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / negative regulation of ubiquitin-dependent protein catabolic process / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / rescue of stalled ribosome / 90S preribosome / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA / positive regulation of translation / small-subunit processome / positive regulation of apoptotic signaling pathway / protein kinase C binding / positive regulation of protein-containing complex assembly / placenta development / cellular response to gamma radiation / mRNA 5'-UTR binding / transcription coactivator binding / modification-dependent protein catabolic process / cytoplasmic ribonucleoprotein granule / spindle / G1/S transition of mitotic cell cycle / rRNA processing / protein tag activity / antimicrobial humoral immune response mediated by antimicrobial peptide / rhythmic process / positive regulation of canonical Wnt signaling pathway / ribosome binding / glucose homeostasis / retina development in camera-type eye / regulation of translation / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cell body / T cell differentiation in thymus / 5S rRNA binding / large ribosomal subunit rRNA binding / perikaryon / cytosolic small ribosomal subunit / defense response to Gram-negative bacterium / killing of cells of another organism / cytosolic large ribosomal subunit / mitochondrial inner membrane / tRNA binding / cytoplasmic translation / postsynaptic density / cell differentiation / protein stabilization / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / ribonucleoprotein complex / cell cycle / translation / positive regulation of protein phosphorylation / positive regulation of apoptotic process / cell division / DNA repair / mRNA binding / apoptotic process / ubiquitin protein ligase binding / synapse / dendrite / positive regulation of cell population proliferation / positive regulation of gene expression / nucleolus / negative regulation of apoptotic process / protein kinase binding / perinuclear region of cytoplasm / Golgi apparatus Similarity search - Function | |||||||||||||||
Biological species | Oryctolagus cuniculus (rabbit) / rabbit (rabbit) / Escherichia coli K-12 (bacteria) / Saccharomyces cerevisiae (brewer's yeast) / Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 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
| |||||||||||||||
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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_26036.map.gz | 1.3 GB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-26036-v30.xml emd-26036.xml | 93.1 KB 93.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26036_fsc.xml | 21 KB | Display | FSC data file |
Images | emd_26036.png | 132.9 KB | ||
Others | emd_26036_half_map_1.map.gz emd_26036_half_map_2.map.gz | 167.6 MB 167.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26036 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26036 | HTTPS FTP |
-Validation report
Summary document | emd_26036_validation.pdf.gz | 732.9 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_26036_full_validation.pdf.gz | 732.5 KB | Display | |
Data in XML | emd_26036_validation.xml.gz | 32.6 KB | Display | |
Data in CIF | emd_26036_validation.cif.gz | 43.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26036 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26036 | HTTPS FTP |
-Related structure data
Related structure data | 7torMC 7tooC 7topC 7toqC 7tosC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_26036.map.gz / Format: CCP4 / Size: 1.4 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Rabbit 80S ribosome with GR20 | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Half map 1
File | emd_26036_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map 2
File | emd_26036_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
+Entire : Mamalian 80S ribosome bound with the ALS/FTD-associated dipeptide...
+Supramolecule #1: Mamalian 80S ribosome bound with the ALS/FTD-associated dipeptide...
+Macromolecule #1: 18S rRNA
+Macromolecule #2: 28S rRNA
+Macromolecule #3: 5.8S rRNA
+Macromolecule #4: 5S rRNA
+Macromolecule #82: tRNAfMet bound to E-site
+Macromolecule #84: mRNA
+Macromolecule #5: 60S ribosomal protein L8
+Macromolecule #6: 60S ribosomal protein L3
+Macromolecule #7: 60S ribosomal protein L4
+Macromolecule #8: 60S ribosomal protein L5
+Macromolecule #9: 60S ribosomal protein L6
+Macromolecule #10: 60S ribosomal protein L7
+Macromolecule #11: eL8
+Macromolecule #12: 60S ribosomal protein L9
+Macromolecule #13: Ribosomal protein L10
+Macromolecule #14: 60S ribosomal protein L11
+Macromolecule #15: uL11
+Macromolecule #16: 60S ribosomal protein L13
+Macromolecule #17: 60S ribosomal protein L14
+Macromolecule #18: 60S ribosomal protein L15
+Macromolecule #19: uL13
+Macromolecule #20: 60S ribosomal protein L17
+Macromolecule #21: eL18
+Macromolecule #22: 60S ribosomal protein L19
+Macromolecule #23: eL20
+Macromolecule #24: 60S ribosomal protein L21
+Macromolecule #25: eL22
+Macromolecule #26: 60S ribosomal protein L23
+Macromolecule #27: Ribosomal protein L24
+Macromolecule #28: uL23
+Macromolecule #29: 60S ribosomal protein L26
+Macromolecule #30: 60S ribosomal protein L27
+Macromolecule #31: 60S ribosomal protein L27a
+Macromolecule #32: eL29
+Macromolecule #33: 60S ribosomal protein L30
+Macromolecule #34: 60S ribosomal protein L31
+Macromolecule #35: 60S ribosomal protein L32
+Macromolecule #36: 60S ribosomal protein L35a
+Macromolecule #37: 60S ribosomal protein L34
+Macromolecule #38: 60S ribosomal protein L35
+Macromolecule #39: 60S ribosomal protein L36
+Macromolecule #40: 60S ribosomal protein L37
+Macromolecule #41: eL38
+Macromolecule #42: 60S ribosomal protein L39
+Macromolecule #43: eL40
+Macromolecule #44: eL41
+Macromolecule #45: eL42
+Macromolecule #46: 60S ribosomal protein L37a
+Macromolecule #47: 60S ribosomal protein L28
+Macromolecule #48: 60S acidic ribosomal protein P0
+Macromolecule #49: Receptor of activated protein C kinase 1
+Macromolecule #50: 40S_SA_C domain-containing protein
+Macromolecule #51: 40S ribosomal protein S3a
+Macromolecule #52: 40S ribosomal protein S2
+Macromolecule #53: 40S ribosomal protein S3
+Macromolecule #54: 40S ribosomal protein S4
+Macromolecule #55: Ribosomal protein S5
+Macromolecule #56: 40S ribosomal protein S6
+Macromolecule #57: eS7
+Macromolecule #58: 40S ribosomal protein S8
+Macromolecule #59: 40S ribosomal protein S9
+Macromolecule #60: 40S ribosomal protein S10
+Macromolecule #61: 40S ribosomal protein S11
+Macromolecule #62: 40S ribosomal protein S12
+Macromolecule #63: 40S ribosomal protein S13
+Macromolecule #64: uS11
+Macromolecule #65: 40S ribosomal protein S15
+Macromolecule #66: uS9
+Macromolecule #67: 40S ribosomal protein S17
+Macromolecule #68: 40S ribosomal protein S18
+Macromolecule #69: eS19
+Macromolecule #70: 40S ribosomal protein S20
+Macromolecule #71: eS21
+Macromolecule #72: 40S ribosomal protein S15a
+Macromolecule #73: 40S ribosomal protein S23
+Macromolecule #74: 40S ribosomal protein S24
+Macromolecule #75: 40S ribosomal protein S25
+Macromolecule #76: eS26
+Macromolecule #77: 40S ribosomal protein S27
+Macromolecule #78: 40S ribosomal protein S28
+Macromolecule #79: 40S ribosomal protein S29
+Macromolecule #80: 40S ribosomal protein S30
+Macromolecule #81: 40S ribosomal protein S27a
+Macromolecule #83: GR20, ALS/FTD dipeptide repeat protein
+Macromolecule #85: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
---|---|
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k 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: 3.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |