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- EMDB-26035: Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptid... -
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Open data
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Basic information
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Title | Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein poly-PR | |||||||||||||||
![]() | Rabbit 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein polyPR | |||||||||||||||
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![]() | ribosomal binding peptide / ALS/FTD-associated dipeptide repeat protein / RIBOSOME | |||||||||||||||
Function / homology | ![]() ribosomal subunit / exit from mitosis / optic nerve development / retinal ganglion cell axon guidance / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / translation regulator activity ...ribosomal subunit / exit from mitosis / optic nerve development / retinal ganglion cell axon guidance / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / translation regulator activity / gastrulation / MDM2/MDM4 family protein binding / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA / small-subunit processome / spindle / mRNA 5'-UTR binding / rRNA processing / rhythmic process / positive regulation of canonical Wnt signaling pathway / regulation of translation / large ribosomal subunit / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / retina development in camera-type eye / small ribosomal subunit / 5S rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / small ribosomal subunit rRNA binding / perikaryon / cytosolic large ribosomal subunit / cytoplasmic translation / cell differentiation / tRNA binding / mitochondrial inner membrane / rRNA binding / ribosome / structural constituent of ribosome / translation / ribonucleoprotein complex / cell division / DNA repair / mRNA binding / apoptotic process / synapse / dendrite / negative regulation of apoptotic process / nucleolus / perinuclear region of cytoplasm / endoplasmic reticulum / Golgi apparatus / DNA binding / RNA binding / zinc ion binding / nucleus / membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||
![]() | Loveland AB / Svidritskiy E / Susorov D / Lee S / Park A / Zvornicanin S / Demo G / Gao FB / Korostelev AA | |||||||||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 794.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 99.5 KB 99.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 20.7 KB | Display | ![]() |
Images | ![]() | 136.3 KB | ||
Filedesc metadata | ![]() | 18.6 KB | ||
Others | ![]() ![]() | 144.7 MB 144.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7toqMC ![]() 7tooC ![]() 7topC ![]() 7torC ![]() 7tosC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Rabbit 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein polyPR | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.87 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half map 2
File | emd_26035_half_map_1.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
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Density Histograms |
-Half map: Half map 1
File | emd_26035_half_map_2.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
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Density Histograms |
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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: RNA (5'-R(*CP*AP*CP*AP*UP*GP*UP*UP*CP*C)-3')
+Macromolecule #84: tRNAfMet
+Macromolecule #5: uL2
+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: uL30
+Macromolecule #11: eL8
+Macromolecule #12: 60S ribosomal protein L9
+Macromolecule #13: Ribosomal protein L10
+Macromolecule #14: 60S ribosomal protein L11
+Macromolecule #15: 60S ribosomal protein L12
+Macromolecule #16: eL13
+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: eL30
+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: eL39
+Macromolecule #43: eL40
+Macromolecule #44: eL41
+Macromolecule #45: eL42
+Macromolecule #46: 60S ribosomal protein L37a
+Macromolecule #47: 60S acidic ribosomal protein P0
+Macromolecule #48: Receptor of activated protein C kinase 1
+Macromolecule #49: 40S_SA_C domain-containing protein
+Macromolecule #50: 40S ribosomal protein S3a
+Macromolecule #51: 40S ribosomal protein S2
+Macromolecule #52: 40S ribosomal protein S3
+Macromolecule #53: 40S ribosomal protein S4
+Macromolecule #54: Ribosomal protein S5
+Macromolecule #55: 40S ribosomal protein S6
+Macromolecule #56: eS7
+Macromolecule #57: 40S ribosomal protein S8
+Macromolecule #58: 40S ribosomal protein S9
+Macromolecule #59: 40S ribosomal protein S10
+Macromolecule #60: 40S ribosomal protein S11
+Macromolecule #61: 40S ribosomal protein S12
+Macromolecule #62: 40S ribosomal protein S13
+Macromolecule #63: 40S ribosomal protein S14
+Macromolecule #64: 40S ribosomal protein S15
+Macromolecule #65: uS9
+Macromolecule #66: 40S ribosomal protein S17
+Macromolecule #67: 40S ribosomal protein S18
+Macromolecule #68: eS19
+Macromolecule #69: 40S ribosomal protein S20
+Macromolecule #70: eS21
+Macromolecule #71: 40S ribosomal protein S15a
+Macromolecule #72: 40S ribosomal protein S23
+Macromolecule #73: 40S ribosomal protein S24
+Macromolecule #74: 40S ribosomal protein S25
+Macromolecule #75: eS26
+Macromolecule #76: 40S ribosomal protein S27
+Macromolecule #77: 40S ribosomal protein S28
+Macromolecule #78: 40S ribosomal protein S29
+Macromolecule #79: 40S ribosomal protein S30
+Macromolecule #80: 40S ribosomal protein S27a
+Macromolecule #81: 60S ribosomal protein L28
+Macromolecule #83: PR20, ALS/FTD dipeptide repeat protein
+Macromolecule #85: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
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: Talos Arctica / Image courtesy: FEI Company |