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- EMDB-44464: 80S ribosome bound with angiogenin and complex of eEF1A and Ala-t... -
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Basic information
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Title | 80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla | |||||||||
![]() | 80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla, main map used for model refinement | |||||||||
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![]() | Angiogenin / RNase / RIBOSOME | |||||||||
Function / homology | ![]() Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / angiogenin-PRI complex / negative regulation of translation in response to stress / tRNA-specific ribonuclease activity / tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis / melatonin binding / tRNA decay / HSF1 activation / signaling ...Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / angiogenin-PRI complex / negative regulation of translation in response to stress / tRNA-specific ribonuclease activity / tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis / melatonin binding / tRNA decay / HSF1 activation / signaling / cell communication / tRNA export from nucleus / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / fungal-type vacuole membrane / Adherens junctions interactions / ribosomal subunit / Protein methylation / oocyte maturation / exit from mitosis / optic nerve development / retinal ganglion cell axon guidance / homeostatic process / hematopoietic stem cell proliferation / rRNA transcription / actin filament bundle assembly / basement membrane / negative regulation of protein phosphorylation / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / endocytic vesicle / translational elongation / phagocytic cup / 90S preribosome / RNA nuclease activity / translation elongation factor activity / positive regulation of phosphorylation / protein-RNA complex assembly / ovarian follicle development / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / translation regulator activity / response to hormone / gastrulation / positive regulation of endothelial cell proliferation / MDM2/MDM4 family protein binding / actin filament polymerization / cytosolic ribosome / Neutrophil degranulation / stress granule assembly / RNA endonuclease activity / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / cellular response to amino acid starvation / cellular response to interleukin-4 / peptide binding / 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 from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / negative regulation of protein kinase activity / positive regulation of protein secretion / maturation of SSU-rRNA / small-subunit processome / placenta development / negative regulation of smooth muscle cell proliferation / spindle / mRNA 5'-UTR binding / cytoplasmic ribonucleoprotein granule / antimicrobial humoral immune response mediated by antimicrobial peptide / cytoplasmic stress granule / rRNA processing / actin filament binding / GDP binding / antibacterial humoral response / rhythmic process / positive regulation of canonical Wnt signaling pathway / cell migration / regulation of translation / large ribosomal subunit / actin cytoskeleton / heparin binding / ribosome binding / actin binding / chromosome / ribosomal small subunit biogenesis / ribosomal small subunit assembly / growth cone / 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 / endonuclease activity / defense response to Gram-negative bacterium / angiogenesis / killing of cells of another organism / perikaryon / cytosolic large ribosomal subunit Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
![]() | Loveland AB / Korostelev AA | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural mechanism of angiogenin activation by the ribosome. Authors: Anna B Loveland / Cha San Koh / Robin Ganesan / Allan Jacobson / Andrei A Korostelev / ![]() Abstract: Angiogenin, an RNase-A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases and epigenetic inheritance. After activation during cellular stress, ...Angiogenin, an RNase-A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases and epigenetic inheritance. After activation during cellular stress, angiogenin cleaves tRNAs at the anticodon loop, resulting in translation repression. However, the catalytic activity of isolated angiogenin is very low, and the mechanisms of the enzyme activation and tRNA specificity have remained a puzzle. Here we identify these mechanisms using biochemical assays and cryogenic electron microscopy (cryo-EM). Our study reveals that the cytosolic ribosome is the activator of angiogenin. A cryo-EM structure features angiogenin bound in the A site of the 80S ribosome. The C-terminal tail of angiogenin is rearranged by interactions with the ribosome to activate the RNase catalytic centre, making the enzyme several orders of magnitude more efficient in tRNA cleavage. Additional 80S-angiogenin structures capture how tRNA substrate is directed by the ribosome into angiogenin's active site, demonstrating that the ribosome acts as the specificity factor. Our findings therefore suggest that angiogenin is activated by ribosomes with a vacant A site, the abundance of which increases during cellular stress. These results may facilitate the development of therapeutics to treat cancer and neurodegenerative diseases. | |||||||||
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) | ![]() ![]() | 111.9 KB 111.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 20.6 KB | Display | ![]() |
Images | ![]() | 191.6 KB | ||
Filedesc metadata | ![]() | 20.1 KB | ||
Others | ![]() ![]() ![]() | 794.8 MB 144.8 MB 144.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9bdpMC ![]() 9bdlC ![]() 9bdnC C: citing same article ( M: atomic model generated by this map |
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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
File | ![]() | ||||||||||||||||||||||||||||||||||||
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Annotation | 80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla, main map used for model refinement | ||||||||||||||||||||||||||||||||||||
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
-Additional map: 80S ribosome bound with angiogenin and complex of...
File | emd_44464_additional_1.map | ||||||||||||
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Annotation | 80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla, map low-passed filtered to 5 A, used for placing tRNA and eEF1A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: 80S ribosome bound with angiogenin and complex of...
File | emd_44464_half_map_1.map | ||||||||||||
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Annotation | 80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla, half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: 80S ribosome bound with angiogenin and complex of...
File | emd_44464_half_map_2.map | ||||||||||||
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Annotation | 80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla, half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : 80S ribosome bound with angiogenin and complex of eEF1A and Ala-t...
+Supramolecule #1: 80S ribosome bound with angiogenin and complex of eEF1A and Ala-t...
+Macromolecule #1: 18S rRNA
+Macromolecule #2: 28S rRNA
+Macromolecule #3: 5.8S rRNA
+Macromolecule #4: 5S rRNA
+Macromolecule #83: tRNAfMet
+Macromolecule #84: mRNA
+Macromolecule #85: tRNAAla
+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: Large ribosomal subunit protein eL8
+Macromolecule #12: 60S ribosomal protein L9
+Macromolecule #13: Ribosomal protein L10
+Macromolecule #14: 60S ribosomal protein L11
+Macromolecule #15: uL11
+Macromolecule #16: Large ribosomal subunit protein eL13
+Macromolecule #17: 60S ribosomal protein L14
+Macromolecule #18: 60S ribosomal protein L15
+Macromolecule #19: Large ribosomal subunit protein uL13
+Macromolecule #20: 60S ribosomal protein L17
+Macromolecule #21: Large ribosomal subunit protein eL18
+Macromolecule #22: 60S ribosomal protein L19
+Macromolecule #23: 60S ribosomal protein L18a
+Macromolecule #24: 60S ribosomal protein L21
+Macromolecule #25: Large ribosomal subunit protein eL22
+Macromolecule #26: 60S ribosomal protein L23
+Macromolecule #27: Ribosomal protein L24
+Macromolecule #28: Large ribosomal subunit protein uL23
+Macromolecule #29: 60S ribosomal protein L26
+Macromolecule #30: 60S ribosomal protein L27
+Macromolecule #31: 60S ribosomal protein L27a
+Macromolecule #32: Large ribosomal subunit protein eL29
+Macromolecule #33: 60S ribosomal protein L30
+Macromolecule #34: 60S ribosomal protein L31
+Macromolecule #35: Large ribosomal subunit protein eL32
+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: Large ribosomal subunit protein eL38
+Macromolecule #42: 60S ribosomal protein L39
+Macromolecule #43: Large ribosomal subunit protein 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: Angiogenin
+Macromolecule #50: Receptor of activated protein C kinase 1
+Macromolecule #51: 40S_SA_C domain-containing protein
+Macromolecule #52: 40S ribosomal protein S3a
+Macromolecule #53: 40S ribosomal protein S2
+Macromolecule #54: 40S ribosomal protein S3
+Macromolecule #55: 40S ribosomal protein S4
+Macromolecule #56: Ribosomal protein S5
+Macromolecule #57: 40S ribosomal protein S6
+Macromolecule #58: Small ribosomal subunit protein eS7
+Macromolecule #59: 40S ribosomal protein S8
+Macromolecule #60: 40S ribosomal protein S9
+Macromolecule #61: 40S ribosomal protein S10
+Macromolecule #62: 40S ribosomal protein S11
+Macromolecule #63: 40S ribosomal protein S12
+Macromolecule #64: 40S ribosomal protein S13
+Macromolecule #65: Small ribosomal subunit protein uS11
+Macromolecule #66: 40S ribosomal protein S15
+Macromolecule #67: Small ribosomal subunit protein uS9
+Macromolecule #68: 40S ribosomal protein S17
+Macromolecule #69: 40S ribosomal protein S18
+Macromolecule #70: Small ribosomal subunit protein eS19
+Macromolecule #71: 40S ribosomal protein S20
+Macromolecule #72: eS21
+Macromolecule #73: 40S ribosomal protein S15a
+Macromolecule #74: 40S ribosomal protein S23
+Macromolecule #75: 40S ribosomal protein S24
+Macromolecule #76: 40S ribosomal protein S25
+Macromolecule #77: eS26
+Macromolecule #78: 40S ribosomal protein S27
+Macromolecule #79: 40S ribosomal protein S28
+Macromolecule #80: 40S ribosomal protein S29
+Macromolecule #81: 40S ribosomal protein S30
+Macromolecule #82: Elongation factor 1-alpha
-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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Grid | Model: Quantifoil R2/1 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |