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- PDB-9bdp: 80S ribosome bound with angiogenin and complex of eEF1A and Ala-t... -
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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 | ||||||
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![]() | RIBOSOME / Angiogenin / RNase | ||||||
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 / Adherens junctions interactions / fungal-type vacuole membrane / Protein methylation / ribosomal subunit / oocyte maturation / exit from mitosis / optic nerve development / retinal ganglion cell axon guidance / homeostatic process / hematopoietic stem cell proliferation / rRNA transcription / positive regulation of signal transduction by p53 class mediator / actin filament bundle assembly / ubiquitin ligase inhibitor activity / basement membrane / phagocytic cup / endocytic vesicle / translational elongation / 90S preribosome / RNA nuclease activity / translation elongation factor activity / protein-RNA complex assembly / positive regulation of phosphorylation / negative regulation of protein phosphorylation / ribosomal small subunit export from nucleus / translation regulator activity / ovarian follicle development / rough endoplasmic reticulum / response to hormone / stress granule assembly / gastrulation / MDM2/MDM4 family protein binding / Neutrophil degranulation / positive regulation of endothelial cell proliferation / cytosolic ribosome / actin filament polymerization / RNA endonuclease activity / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / cellular response to interleukin-4 / cellular response to amino acid starvation / peptide binding / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / positive regulation of protein secretion / negative regulation of protein kinase activity / small-subunit processome / placenta development / positive regulation of apoptotic signaling pathway / negative regulation of smooth muscle cell proliferation / spindle / cytoplasmic ribonucleoprotein granule / mRNA 5'-UTR binding / rRNA processing / cytoplasmic stress granule / actin filament binding / cell migration / antimicrobial humoral immune response mediated by antimicrobial peptide / GDP binding / positive regulation of canonical Wnt signaling pathway / actin cytoskeleton / rhythmic process / antibacterial humoral response / regulation of translation / large ribosomal subunit / heparin binding / ribosome binding / chromosome / actin binding / ribosomal small subunit assembly / ribosomal small subunit biogenesis / retina development in camera-type eye / growth cone / small ribosomal subunit / small ribosomal subunit rRNA binding / 5S rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / angiogenesis / endonuclease activity / defense response to Gram-negative bacterium / perikaryon / cytosolic large ribosomal subunit / killing of cells of another organism Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
![]() | Loveland, A.B. / Korostelev, A.A. | ||||||
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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 4.8 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2 MB | Display | ![]() |
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Full document | ![]() | 2.1 MB | Display | |
Data in XML | ![]() | 352.4 KB | Display | |
Data in CIF | ![]() | 616.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-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 ![]() |
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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.) ![]() |
#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.) ![]() ![]() ![]() 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: ![]() |
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
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 |