7nwi

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Mammalian pre-termination 80S ribosome with Empty-A site bound by Blasticidin S

Structural highlights

7nwi 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 3.13Å
Ligands:BLS, MG, ZN
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

Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding to the peptidyl transferase center of the large ribosomal subunit. Using biochemical, structural and cellular approaches, we show here that BlaS inhibits both translation elongation and termination in Mammalia. Bound to mammalian terminating ribosomes, BlaS distorts the 3'CCA tail of the P-site tRNA to a larger extent than previously reported for bacterial ribosomes, thus delaying both, peptide bond formation and peptidyl-tRNA hydrolysis. While BlaS does not inhibit stop codon recognition by the eukaryotic release factor 1 (eRF1), it interferes with eRF1's accommodation into the peptidyl transferase center and subsequent peptide release. In human cells, BlaS inhibits nonsense-mediated mRNA decay and, at subinhibitory concentrations, modulates translation dynamics at premature termination codons leading to enhanced protein production.

Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA.,Powers KT, Stevenson-Jones F, Yadav SKN, Amthor B, Bufton JC, Borucu U, Shen D, Becker JP, Lavysh D, Hentze MW, Kulozik AE, Neu-Yilik G, Schaffitzel C Nucleic Acids Res. 2021 Jul 21;49(13):7665-7679. doi: 10.1093/nar/gkab532. PMID:34157102[5]

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

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Citations
1 reviews cite this structure
No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors.
Mailliot et al. (2022)
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5 other articles
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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ Powers KT, Stevenson-Jones F, Yadav SKN, Amthor B, Bufton JC, Borucu U, Shen D, Becker JP, Lavysh D, Hentze MW, Kulozik AE, Neu-Yilik G, Schaffitzel C. Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA. Nucleic Acids Res. 2021 Jul 21;49(13):7665-7679. doi: 10.1093/nar/gkab532. PMID:34157102 doi:http://dx.doi.org/10.1093/nar/gkab532

Contents


PDB ID 7nwi

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