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- EMDB-44458: 80S ribosome with angiogenin, in vitro assembled complex without ... -
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Open data
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Basic information
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Title | 80S ribosome with angiogenin, in vitro assembled complex without substrate tRNA | |||||||||
![]() | 80S ribosome with angiogenin, in vitro assembled complex without substrate tRNA | |||||||||
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![]() | Angiogenin / RNase / RIBOSOME | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.04 Å | |||||||||
![]() | Loveland AB / Korostelev AA | |||||||||
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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 794.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.6 KB 15.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 20.3 KB | Display | ![]() |
Images | ![]() | 102.5 KB | ||
Filedesc metadata | ![]() | 4.3 KB | ||
Others | ![]() ![]() | 144.4 MB 144.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 867.7 KB | Display | ![]() |
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Full document | ![]() | 867.2 KB | Display | |
Data in XML | ![]() | 29.8 KB | Display | |
Data in CIF | ![]() | 39.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | 80S ribosome with angiogenin, in vitro assembled complex without substrate tRNA | ||||||||||||||||||||||||||||||||||||
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
-Half map: 80S ribosome with angiogenin, in vitro assembled complex...
File | emd_44458_half_map_1.map | ||||||||||||
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Annotation | 80S ribosome with angiogenin, in vitro assembled complex without substrate tRNA, half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: 80S ribosome with angiogenin, in vitro assembled complex...
File | emd_44458_half_map_2.map | ||||||||||||
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Annotation | 80S ribosome with angiogenin, in vitro assembled complex without substrate tRNA, half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : 80S ribosome with angiogenin assembled in vitro without substrate tRNA
Entire | Name: 80S ribosome with angiogenin assembled in vitro without substrate tRNA |
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Components |
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-Supramolecule #1: 80S ribosome with angiogenin assembled in vitro without substrate tRNA
Supramolecule | Name: 80S ribosome with angiogenin assembled in vitro without substrate tRNA type: complex / ID: 1 / Parent: 0 |
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Molecular weight | Theoretical: 4.5 MDa |
-Supramolecule #2: 80S ribosome
Supramolecule | Name: 80S ribosome / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: angiogenin
Supramolecule | Name: angiogenin / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #4: tRNA-fMet
Supramolecule | Name: tRNA-fMet / type: complex / ID: 4 / Parent: 1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #5: mRNA
Supramolecule | Name: mRNA / type: complex / ID: 5 / Parent: 1 |
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Source (natural) | Organism: ![]() |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7 |
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Grid | Model: Quantifoil R2/1 / Material: COPPER / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV |
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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: ![]() |
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 |