+
Open data
-
Basic information
Entry | Database: PDB / ID: 9bdn | ||||||
---|---|---|---|---|---|---|---|
Title | 80S ribosome with angiogenin and tRNAAla | ||||||
![]() |
| ||||||
![]() | RIBOSOME / Angiogenin / RNase | ||||||
Function / homology | ![]() 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 biogenesis / 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 Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
![]() | Loveland, A.B. / Korostelev, A.A. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() 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 |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 4.8 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.8 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.9 MB | Display | |
Data in XML | ![]() | 334.8 KB | Display | |
Data in CIF | ![]() | 596.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 44463MC ![]() 9bdlC ![]() 9bdpC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
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) ![]() ![]() | ||||
---|---|---|---|---|---|
#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) ![]() ![]() | ||||
#82: RNA chain | Mass: 24802.785 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #83: RNA chain | | Mass: 8591.155 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() #84: RNA chain | | Mass: 24486.477 Da / Num. of mol.: 1 / Source method: obtained synthetically Details: in vitro transcribed yeast tRNAAla with non-templated CCA added Source: (synth.) ![]() ![]() |
+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) ![]() ![]() |
---|---|
#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) ![]() ![]() |
---|---|
#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 , 8 types, 8 molecules AL12AL42ALP0ANGARACAS00AS21AS26
#15: Protein | Mass: 16561.117 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
---|---|
#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) ![]() ![]() |
-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) ![]() ![]() |
---|
+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) ![]() ![]() |
---|---|
#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) ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: 80S ribosome with angiogenin and tRNAAla / Type: RIBOSOME / Entity ID: all / Source: MULTIPLE SOURCES |
---|---|
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 |
---|---|
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) |
-
Processing
EM software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 273774 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 17593 / Num. of class averages: 5 / Symmetry type: POINT |