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Yorodumi- PDB-9bdp: 80S ribosome bound with angiogenin and complex of eEF1A and Ala-t... -
+Open data
-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 information Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 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 / melatonin binding / HSF1 activation / cell communication ...Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 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 / melatonin binding / HSF1 activation / cell communication / tRNA export from nucleus / ribosomal subunit / negative regulation of formation of translation preinitiation complex / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / fungal-type vacuole membrane / Protein methylation / 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 / retinal ganglion cell axon guidance / homeostatic process / mammalian oogenesis stage / G1 to G0 transition / macrophage chemotaxis / activation-induced cell death of T cells / lung morphogenesis / rRNA transcription / actin filament bundle assembly / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / translational elongation / basement membrane / 90S preribosome / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / T cell proliferation involved in immune response / RNA nuclease activity / protein-RNA complex assembly / erythrocyte development / translation elongation factor activity / cellular response to actinomycin D / negative regulation of ubiquitin-dependent protein catabolic process / ribosomal small subunit export from nucleus / translation regulator activity / positive regulation of phosphorylation / ovarian follicle development / 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 / maturation of LSU-rRNA / positive regulation of endothelial cell proliferation / Neutrophil degranulation / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / cytosolic ribosome / activation of protein kinase B activity / actin filament polymerization / RNA endonuclease activity / cellular response to amino acid starvation / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / response to hormone / rescue of stalled ribosome / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / negative regulation of protein phosphorylation / cellular response to leukemia inhibitory factor / positive regulation of protein secretion / small-subunit processome / positive regulation of translation / protein kinase C binding / positive regulation of apoptotic signaling pathway / negative regulation of smooth muscle cell proliferation / negative regulation of protein kinase activity / peptide binding / positive regulation of protein-containing complex assembly / placenta development / cellular response to gamma radiation / transcription coactivator binding / cellular response to type II interferon / mRNA 5'-UTR binding / spindle / cytoplasmic ribonucleoprotein granule / G1/S transition of mitotic cell cycle / rRNA processing / ribosomal small subunit biogenesis / GDP binding / actin filament binding / antimicrobial humoral immune response mediated by antimicrobial peptide / small ribosomal subunit rRNA binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Saccharomyces cerevisiae (brewer's yeast) Oryctolagus cuniculus (rabbit) Escherichia coli (E. coli) | ||||||
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: 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-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
Summary document | 9bdp_validation.pdf.gz | 2 MB | Display | wwPDB validaton report |
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Full document | 9bdp_full_validation.pdf.gz | 2.1 MB | Display | |
Data in XML | 9bdp_validation.xml.gz | 352.4 KB | Display | |
Data in CIF | 9bdp_validation.cif.gz | 616.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bd/9bdp ftp://data.pdbj.org/pub/pdb/validation_reports/bd/9bdp | HTTPS FTP |
-Related structure data
Related structure data | 44464MC 9bdlC 9bdnC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-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) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte | ||||
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#2: RNA chain | Mass: 1166972.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte | ||||
#3: RNA chain | Mass: 50143.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte | ||||
#4: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: GenBank: X06789.1 | ||||
#83: RNA chain | Mass: 24802.785 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 1848934315 #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.) Saccharomyces cerevisiae (brewer's yeast) Production host: Escherichia coli (E. coli) / References: GenBank: 1163001469 |
+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) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1STW0 |
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#16: Protein | Mass: 24200.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TKB3 |
#19: Protein | Mass: 23144.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TVS8 |
#21: Protein | Mass: 21568.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TFE0 |
#25: Protein | Mass: 11495.275 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TSG1 |
#28: Protein | Mass: 13727.181 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1SE76 |
#32: Protein | Mass: 26708.707 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1SGR6 |
#35: Protein | Mass: 15022.021 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TUN8 |
#41: Protein | Mass: 8107.752 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1U001 |
#43: Protein | Mass: 6199.574 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: P0DXC2 |
-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) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: B7NZQ2 |
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#27: Protein | Mass: 14131.536 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1SE28 |
#56: Protein | Mass: 21525.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TFM5 |
-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) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1SMR7 |
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#45: Protein | Mass: 12198.603 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: A0A5F9D391 |
#48: Protein | Mass: 21521.062 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1SPK4 |
#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: Escherichia coli (E. coli) 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) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1SJB4 |
#51: Protein | Mass: 24361.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TJH8 |
#72: Protein | Mass: 9124.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TM82 |
#77: Protein | Mass: 11645.794 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TFE8 |
#82: Protein | Mass: 50110.621 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Saccharomyces cerevisiae (brewer's yeast) / Strain: BJ2168 / References: UniProt: P02994 |
-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) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: A0A087WNH4 |
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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) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1SVB0 |
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#65: Protein | Mass: 14431.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1T1F0 |
#67: Protein | Mass: 16032.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1SGX4 |
#70: Protein | Mass: 15611.003 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / Tissue: Reticulocyte / References: UniProt: G1TN62 |
-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 |
-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 |
-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) |
-Processing
EM software |
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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 |