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Yorodumi- PDB-9bdp: 80S ribosome bound with angiogenin and complex of eEF1A and Ala-t... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9bdp | ||||||
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| Title | 80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla | ||||||
Components |
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Keywords | RIBOSOME / Angiogenin / RNase | ||||||
| Function / homology | Function and homology informationEukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / angiogenin-PRI complex / tRNA-specific ribonuclease activity / negative regulation of translation in response to stress / tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis / tRNA decay / melatonin binding / HSF1 activation / signaling ...Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / angiogenin-PRI complex / tRNA-specific ribonuclease activity / negative regulation of translation in response to stress / tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis / tRNA decay / melatonin binding / HSF1 activation / signaling / cell communication / tRNA export from nucleus / ribosomal subunit / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / fungal-type vacuole membrane / Protein methylation / Adherens junctions interactions / oocyte maturation / hematopoietic stem cell proliferation / homeostatic process / negative regulation of protein phosphorylation / rRNA transcription / basement membrane / actin filament bundle assembly / positive regulation of phosphorylation / translational elongation / RNA nuclease activity / endocytic vesicle / ubiquitin ligase inhibitor activity / 90S preribosome / positive regulation of signal transduction by p53 class mediator / translation elongation factor activity / negative regulation of protein kinase activity / ovarian follicle development / phagocytic cup / protein-RNA complex assembly / response to hormone / positive regulation of endothelial cell proliferation / rough endoplasmic reticulum / actin filament polymerization / ribosomal small subunit export from nucleus / translation regulator activity / Neutrophil degranulation / gastrulation / peptide binding / MDM2/MDM4 family protein binding / RNA endonuclease activity / stress granule assembly / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / cellular response to amino acid starvation / placenta development / DNA-(apurinic or apyrimidinic site) lyase / ribosomal large subunit biogenesis / positive regulation of protein secretion / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / negative regulation of smooth muscle cell proliferation / small-subunit processome / spindle / cytoplasmic stress granule / cytoplasmic ribonucleoprotein granule / rRNA processing / actin filament binding / GDP binding / cell migration / positive regulation of canonical Wnt signaling pathway / rhythmic process / antimicrobial humoral immune response mediated by antimicrobial peptide / actin cytoskeleton / heparin binding / regulation of translation / large ribosomal subunit / antibacterial humoral response / chromosome / ribosome binding / actin binding / growth cone / ribosomal small subunit biogenesis / ribosomal small subunit assembly / ribosomal large subunit assembly / 5S rRNA binding / small ribosomal subunit / small ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / angiogenesis / endonuclease activity / cytosolic large ribosomal subunit / killing of cells of another organism / defense response to Gram-negative bacterium / perikaryon / cytoskeleton / response to hypoxia / cytoplasmic translation / cell differentiation / tRNA binding / mitochondrial inner membrane Similarity search - Function | ||||||
| Biological species | Homo sapiens (human)![]() ![]() ![]() | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
Authors | Loveland, A.B. / Korostelev, A.A. | ||||||
| Funding support | United States, 1items
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Citation | Journal: Nature / Year: 2024Title: 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. | ||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9bdp.cif.gz | 4.8 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb9bdp.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9bdp.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bd/9bdp ftp://data.pdbj.org/pub/pdb/validation_reports/bd/9bdp | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 44464MC ![]() 9bdlC ![]() 9bdnC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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| 1 |
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Components
-RNA chain , 7 types, 8 molecules A18SA28SA58SA5SETRNPTRNMRNATIRN
| #1: RNA chain | Mass: 602777.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||
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| #2: RNA chain | Mass: 1166972.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||
| #3: RNA chain | Mass: 50143.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||
| #4: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||
| #83: RNA chain | Mass: 24802.785 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #84: RNA chain | | Mass: 8591.155 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)#85: RNA chain | | Mass: 24486.477 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() |
+60S ribosomal protein ... , 28 types, 28 molecules AL02AL03AL04AL05AL06AL07AL09AL11AL14AL15AL17AL19AL20AL21AL23AL26AL27AL28AL30AL31AL33AL34AL35AL36AL37AL39AL43ALNW
-Large ribosomal subunit protein ... , 10 types, 10 molecules AL08AL13AL16AL18AL22AL25AL29AL32AL38AL40
| #11: Protein | Mass: 27351.377 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #16: Protein | Mass: 24200.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #19: Protein | Mass: 23144.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #21: Protein | Mass: 21568.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #25: Protein | Mass: 11495.275 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #28: Protein | Mass: 13727.181 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #32: Protein | Mass: 26708.707 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #35: Protein | Mass: 15022.021 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #41: Protein | Mass: 8107.752 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #43: Protein | Mass: 6199.574 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Ribosomal protein ... , 3 types, 3 molecules AL10AL24AS05
| #13: Protein | Mass: 24511.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #27: Protein | Mass: 14131.536 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #56: Protein | Mass: 21525.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 9 types, 9 molecules AL12AL42ALP0ANGARACAS00AS21AS26EF1A
| #15: Protein | Mass: 16561.117 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #45: Protein | Mass: 12198.603 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #48: Protein | Mass: 21521.062 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #49: Protein | Mass: 16576.117 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANG, RNASE5 / Production host: ![]() References: UniProt: P03950, Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters |
| #50: Protein | Mass: 34669.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #51: Protein | Mass: 24361.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #72: Protein | Mass: 9124.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #77: Protein | Mass: 11645.794 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #82: Protein | Mass: 50110.621 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein/peptide , 1 types, 1 molecules AL41
| #44: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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+40S ribosomal protein ... , 23 types, 23 molecules AS01AS02AS03AS04AS06AS08AS09AS10AS11AS12AS13AS15AS17AS18AS20AS22AS23AS24AS25AS27AS28AS29AS30
-Small ribosomal subunit protein ... , 4 types, 4 molecules AS07AS14AS16AS19
| #58: Protein | Mass: 21629.309 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #65: Protein | Mass: 14431.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #67: Protein | Mass: 16032.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #70: Protein | Mass: 15611.003 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Details
| Has protein modification | Y |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: 80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla Type: RIBOSOME / Entity ID: all / Source: MULTIPLE SOURCES |
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| Molecular weight | Value: 4.5 MDa / Experimental value: NO |
| Buffer solution | pH: 7 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Grid type: Quantifoil R2/1 |
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 278 K |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TALOS ARCTICA |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
| Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
| Particle selection | Num. of particles selected: 273774 | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 3604 / Num. of class averages: 1 / Symmetry type: POINT |
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Homo sapiens (human)



United States, 1items
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FIELD EMISSION GUN