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-Structure paper
タイトル | Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA. |
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ジャーナル・号・ページ | Nucleic Acids Res, Vol. 49, Issue 13, Page 7665-7679, Year 2021 |
掲載日 | 2021年7月21日 |
著者 | Kyle T Powers / Flint Stevenson-Jones / Sathish K N Yadav / Beate Amthor / Joshua C Bufton / Ufuk Borucu / Dakang Shen / Jonas P Becker / Daria Lavysh / Matthias W Hentze / Andreas E Kulozik / Gabriele Neu-Yilik / Christiane Schaffitzel / |
PubMed 要旨 | 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 ...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. |
リンク | Nucleic Acids Res / PubMed:34157102 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.13 - 4.1 Å |
構造データ | EMDB-12631, PDB-7nwg: EMDB-12632, PDB-7nwh: EMDB-12633, PDB-7nwi: |
化合物 | ChemComp-MG: ChemComp-BLS: ChemComp-ZN: ChemComp-GCP: |
由来 |
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キーワード | RIBOSOME / Inhibitor 80S Termination Complex Blasticidin S Translation NMD |