7NWG

Mammalian pre-termination 80S ribosome with Hybrid P/E- and A/P-site tRNA's bound by Blasticidin S.

これはPDB形式変換不可エントリーです。

7NWG の概要

• エントリーDOI: 10.2210/pdb7nwg/pdb
• EMDBエントリー: 12631
• 分子名称: 28S Ribosomal RNA, Ribosomal protein S5, 40S ribosomal protein S6, ... (89 entities in total)
• 機能のキーワード: inhibitor 80s termination complex blasticidin s translation nmd, ribosome
• 由来する生物種: Oryctolagus cuniculus; 詳細
• タンパク質・核酸の鎖数: 86
• 化学式量合計: 3512377.55

構造登録者

Powers, K.T.,Yadav, S.K.N.,Bufton, J.C.,Schaffitzel, C. (登録日: 2021-03-16, 公開日: 2021-07-07, 最終更新日: 2024-11-06)

主引用文献

Powers, K.T.,Stevenson-Jones, F.,Yadav, S.K.N.,Amthor, B.,Bufton, J.C.,Borucu, U.,Shen, D.,Becker, J.P.,Lavysh, D.,Hentze, M.W.,Kulozik, A.E.,Neu-Yilik, G.,Schaffitzel, C.
Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA.
Nucleic Acids Res., 49:7665-7679, 2021

PubMed Abstract: 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.

PubMed: 34157102
DOI: 10.1093/nar/gkab532

実験手法

ELECTRON MICROSCOPY (3.8 Å)