9bdp

From Proteopedia

(Difference between revisions)

Current revision

80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla

Structural highlights

9bdp is a 10 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RL8_RABIT Component of the large ribosomal subunit (PubMed:25601755, PubMed:26245381, PubMed:27863242, PubMed:30517857). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:25601755, PubMed:26245381, PubMed:27863242, PubMed:30517857).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Angiogenin, an RNase-A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases and epigenetic inheritance(1-10). After activation during cellular stress, angiogenin cleaves tRNAs at the anticodon loop, resulting in translation repression(11-15). However, the catalytic activity of isolated angiogenin is very low, and the mechanisms of the enzyme activation and tRNA specificity have remained a puzzle(3,16-23). 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(24-27). These results may facilitate the development of therapeutics to treat cancer and neurodegenerative diseases.

Structural mechanism of angiogenin activation by the ribosome.,Loveland AB, Koh CS, Ganesan R, Jacobson A, Korostelev AA Nature. 2024 Jun;630(8017):769-776. doi: 10.1038/s41586-024-07508-8. Epub 2024 , May 8. PMID:38718836^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Muhs M, Hilal T, Mielke T, Skabkin MA, Sanbonmatsu KY, Pestova TV, Spahn CM. Cryo-EM of Ribosomal 80S Complexes with Termination Factors Reveals the Translocated Cricket Paralysis Virus IRES. Mol Cell. 2015 Feb 5;57(3):422-432. doi: 10.1016/j.molcel.2014.12.016. Epub 2015 , Jan 15. PMID:25601755 doi:http://dx.doi.org/10.1016/j.molcel.2014.12.016
↑ Brown A, Shao S, Murray J, Hegde RS, Ramakrishnan V. Structural basis for stop codon recognition in eukaryotes. Nature. 2015 Aug 27;524(7566):493-6. doi: 10.1038/nature14896. Epub 2015 Aug 5. PMID:26245381 doi:http://dx.doi.org/10.1038/nature14896
↑ Shao S, Murray J, Brown A, Taunton J, Ramakrishnan V, Hegde RS. Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes. Cell. 2016 Nov 17;167(5):1229-1240.e15. doi: 10.1016/j.cell.2016.10.046. PMID:27863242 doi:http://dx.doi.org/10.1016/j.cell.2016.10.046
↑ Flis J, Holm M, Rundlet EJ, Loerke J, Hilal T, Dabrowski M, Burger J, Mielke T, Blanchard SC, Spahn CMT, Budkevich TV. tRNA Translocation by the Eukaryotic 80S Ribosome and the Impact of GTP Hydrolysis. Cell Rep. 2018 Dec 4;25(10):2676-2688.e7. doi: 10.1016/j.celrep.2018.11.040. PMID:30517857 doi:http://dx.doi.org/10.1016/j.celrep.2018.11.040
↑ Loveland AB, Koh CS, Ganesan R, Jacobson A, Korostelev AA. Structural mechanism of angiogenin activation by the ribosome. Nature. 2024 Jun;630(8017):769-776. PMID:38718836 doi:10.1038/s41586-024-07508-8

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9bdp"

Categories: Large Structures | Oryctolagus cuniculus | Korostelev AA | Loveland AB

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9bdp is ON HOLD
+==80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla==
+<StructureSection load='9bdp' size='340' side='right'caption='[[9bdp]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9bdp]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BDP FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9bdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bdp OCA], [https://pdbe.org/9bdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bdp RCSB], [https://www.ebi.ac.uk/pdbsum/9bdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bdp ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/RL8_RABIT RL8_RABIT] Component of the large ribosomal subunit (PubMed:25601755, PubMed:26245381, PubMed:27863242, PubMed:30517857). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:25601755, PubMed:26245381, PubMed:27863242, PubMed:30517857).<ref>PMID:25601755</ref> <ref>PMID:26245381</ref> <ref>PMID:27863242</ref> <ref>PMID:30517857</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Angiogenin, an RNase-A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases and epigenetic inheritance(1-10). After activation during cellular stress, angiogenin cleaves tRNAs at the anticodon loop, resulting in translation repression(11-15). However, the catalytic activity of isolated angiogenin is very low, and the mechanisms of the enzyme activation and tRNA specificity have remained a puzzle(3,16-23). 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(24-27). These results may facilitate the development of therapeutics to treat cancer and neurodegenerative diseases.
-Authors:
+Structural mechanism of angiogenin activation by the ribosome.,Loveland AB, Koh CS, Ganesan R, Jacobson A, Korostelev AA Nature. 2024 Jun;630(8017):769-776. doi: 10.1038/s41586-024-07508-8. Epub 2024 , May 8. PMID:38718836<ref>PMID:38718836</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9bdp" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Oryctolagus cuniculus]]
+[[Category: Korostelev AA]]
+[[Category: Loveland AB]]

9bdp

From Proteopedia

Current revision

80S ribosome bound with angiogenin and complex of eEF1A and Ala-tRNAAla

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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