8EKC

Escherichia coli 70S ribosome bound to thermorubin, deacylated P-site tRNAfMet and aminoacylated A-site Phe-tRNA

これはPDB形式変換不可エントリーです。

8EKC の概要

• エントリーDOI: 10.2210/pdb8ekc/pdb
• EMDBエントリー: 28197
• 分子名称: 16S Ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (60 entities in total)
• 機能のキーワード: antibiotic, thermorubin, cryo-em, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 55
• 化学式量合計: 2213155.19

構造登録者

Rybak, M.Y.,Gagnon, M.G. (登録日: 2022-09-20, 公開日: 2022-12-07, 最終更新日: 2025-03-19)

主引用文献

Paranjpe, M.N.,Marina, V.I.,Grachev, A.A.,Maviza, T.P.,Tolicheva, O.A.,Paleskava, A.,Osterman, I.A.,Sergiev, P.V.,Konevega, A.L.,Polikanov, Y.S.,Gagnon, M.G.
Insights into the molecular mechanism of translation inhibition by the ribosome-targeting antibiotic thermorubin.
Nucleic Acids Res., 51:449-462, 2023

PubMed Abstract: Thermorubin (THR) is an aromatic anthracenopyranone antibiotic active against both Gram-positive and Gram-negative bacteria. It is known to bind to the 70S ribosome at the intersubunit bridge B2a and was thought to inhibit factor-dependent initiation of translation and obstruct the accommodation of tRNAs into the A site. Here, we show that thermorubin causes ribosomes to stall in vivo and in vitro at internal and termination codons, thereby allowing the ribosome to initiate protein synthesis and translate at least a few codons before stalling. Our biochemical data show that THR affects multiple steps of translation elongation with a significant impact on the binding stability of the tRNA in the A site, explaining premature cessation of translation. Our high-resolution crystal and cryo-EM structures of the 70S-THR complex show that THR can co-exist with P- and A-site tRNAs, explaining how ribosomes can elongate in the presence of the drug. Remarkable is the ability of THR to arrest ribosomes at the stop codons. Our data suggest that by causing structural re-arrangements in the decoding center, THR interferes with the accommodation of tRNAs or release factors into the ribosomal A site.

PubMed: 36546783
DOI: 10.1093/nar/gkac1189

実験手法

ELECTRON MICROSCOPY (2.7 Å)