+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-44461 | |||||||||
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Title | 80S ribosome with angiogenin | |||||||||
Map data | 80S ribosome with angiogenin | |||||||||
Sample |
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Keywords | Angiogenin / RNase / RIBOSOME | |||||||||
Function / homology | Function and homology information activation of phospholipase A2 activity / angiogenin-PRI complex / diacylglycerol biosynthetic process / tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis / tRNA decay / cell communication / negative regulation of formation of translation preinitiation complex / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / Adherens junctions interactions / GAIT complex ...activation of phospholipase A2 activity / angiogenin-PRI complex / diacylglycerol biosynthetic process / tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis / tRNA decay / cell communication / negative regulation of formation of translation preinitiation complex / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / Adherens junctions interactions / GAIT complex / oocyte maturation / 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 / homeostatic process / activation-induced cell death of T cells / lung morphogenesis / macrophage chemotaxis / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / rRNA transcription / phagocytic cup / : / basement membrane / 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 / protein-RNA complex assembly / RNA nuclease activity / ribosomal small subunit export from nucleus / erythrocyte development / translation regulator activity / cellular response to actinomycin D / cytosolic ribosome / ovarian follicle development / rough endoplasmic reticulum / positive regulation of phosphorylation / 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 / positive regulation of endothelial cell proliferation / RNA endonuclease activity / 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 / activation of protein kinase B activity / actin filament polymerization / 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) / response to hormone / maturation of LSU-rRNA / ribosomal large subunit biogenesis / cellular response to leukemia inhibitory factor / maturation of SSU-rRNA / positive regulation of translation / positive regulation of protein secretion / small-subunit processome / positive regulation of apoptotic signaling pathway / protein kinase C binding / peptide binding / negative regulation of smooth muscle cell proliferation / positive regulation of protein-containing complex assembly / placenta development / cellular response to gamma radiation / mRNA 5'-UTR binding / transcription coactivator binding / cellular response to type II interferon / cytoplasmic ribonucleoprotein granule / spindle / G1/S transition of mitotic cell cycle / rRNA processing / antimicrobial humoral immune response mediated by antimicrobial peptide / rhythmic process / actin cytoskeleton / positive regulation of canonical Wnt signaling pathway / cell migration / ribosome binding / glucose homeostasis / retina development in camera-type eye / regulation of translation / chromosome / heparin binding / ribosomal small subunit biogenesis / actin binding / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cell body / antibacterial humoral response / growth cone Similarity search - Function | |||||||||
Biological species | Oryctolagus cuniculus (rabbit) / Homo sapiens (human) / Escherichia coli K-12 (bacteria) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Loveland AB / Korostelev AA | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2024 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 | emd_44461.map.gz | 794.4 MB | EMDB map data format | |
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Header (meta data) | emd-44461-v30.xml emd-44461.xml | 115.6 KB 115.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_44461_fsc.xml | 20.6 KB | Display | FSC data file |
Images | emd_44461.png | 182.9 KB | ||
Filedesc metadata | emd-44461.cif.gz | 19.4 KB | ||
Others | emd_44461_additional_1.map.gz emd_44461_half_map_1.map.gz emd_44461_half_map_2.map.gz | 794.3 MB 144.9 MB 144.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-44461 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44461 | HTTPS FTP |
-Validation report
Summary document | emd_44461_validation.pdf.gz | 867.3 KB | Display | EMDB validaton report |
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Full document | emd_44461_full_validation.pdf.gz | 866.9 KB | Display | |
Data in XML | emd_44461_validation.xml.gz | 29.7 KB | Display | |
Data in CIF | emd_44461_validation.cif.gz | 40 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44461 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44461 | HTTPS FTP |
-Related structure data
Related structure data | 9bdlMC 9bdnC 9bdpC 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_44461.map.gz / Format: CCP4 / Size: 857.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | 80S ribosome with angiogenin | ||||||||||||||||||||||||||||||||||||
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 with angiogenin, sharpened with B-factor -50 A2
File | emd_44461_additional_1.map | ||||||||||||
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Annotation | 80S ribosome with angiogenin, sharpened with B-factor -50 A2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: 80S ribosome with angiogenin, half map 1
File | emd_44461_half_map_1.map | ||||||||||||
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Annotation | 80S ribosome with angiogenin, half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: 80S ribosome with angiogenin, half map 2
File | emd_44461_half_map_2.map | ||||||||||||
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Annotation | 80S ribosome with angiogenin, half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : 80S ribosome with angiogenin
+Supramolecule #1: 80S ribosome with angiogenin
+Supramolecule #2: 80S ribosome
+Supramolecule #3: angiogenin
+Supramolecule #4: mRNA
+Supramolecule #5: tRNAfMet
+Macromolecule #1: 18S rRNA
+Macromolecule #2: 28S rRNA
+Macromolecule #3: 5.8S rRNA
+Macromolecule #4: 5S rRNA
+Macromolecule #80: tRNAfMet
+Macromolecule #81: Model mRNA
+Macromolecule #5: 60S ribosomal protein L8
+Macromolecule #6: 60S ribosomal protein L3
+Macromolecule #7: 60S ribosomal protein L4
+Macromolecule #8: Large ribosomal subunit protein uL18
+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: Large ribosomal subunit protein eL13
+Macromolecule #16: Large ribosomal subunit protein eL14
+Macromolecule #17: 60S ribosomal protein L15
+Macromolecule #18: Large ribosomal subunit protein uL13
+Macromolecule #19: 60S ribosomal protein L17
+Macromolecule #20: Large ribosomal subunit protein eL18
+Macromolecule #21: 60S ribosomal protein L19
+Macromolecule #22: 60S ribosomal protein L18a
+Macromolecule #23: 60S ribosomal protein L21
+Macromolecule #24: Large ribosomal subunit protein eL22
+Macromolecule #25: 60S ribosomal protein L23
+Macromolecule #26: Ribosomal protein L24
+Macromolecule #27: Large ribosomal subunit protein uL23
+Macromolecule #28: 60S ribosomal protein L26
+Macromolecule #29: 60S ribosomal protein L27
+Macromolecule #30: 60S ribosomal protein L27a
+Macromolecule #31: Large ribosomal subunit protein eL29
+Macromolecule #32: 60S ribosomal protein L30
+Macromolecule #33: 60S ribosomal protein L31
+Macromolecule #34: Large ribosomal subunit protein eL32
+Macromolecule #35: 60S ribosomal protein L35a
+Macromolecule #36: 60S ribosomal protein L34
+Macromolecule #37: 60S ribosomal protein L35
+Macromolecule #38: 60S ribosomal protein L36
+Macromolecule #39: 60S ribosomal protein L37
+Macromolecule #40: Large ribosomal subunit protein eL38
+Macromolecule #41: 60S ribosomal protein L39
+Macromolecule #42: Large ribosomal subunit protein eL40
+Macromolecule #43: eL41
+Macromolecule #44: eL42
+Macromolecule #45: 60S ribosomal protein L37a
+Macromolecule #46: 60S ribosomal protein L28
+Macromolecule #47: Angiogenin
+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: Small ribosomal subunit protein 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: Small ribosomal subunit protein uS11
+Macromolecule #64: 40S ribosomal protein S15
+Macromolecule #65: Small ribosomal subunit protein uS9
+Macromolecule #66: 40S ribosomal protein S17
+Macromolecule #67: 40S ribosomal protein S18
+Macromolecule #68: Small ribosomal subunit protein 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
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
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Grid | Model: Quantifoil R2/1 / Material: COPPER / 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 |
-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: FIELD EMISSION GUN |
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 |