8SCB

Terminating ribosome with SRI-41315

これはPDB形式変換不可エントリーです。

8SCB の概要

• エントリーDOI: 10.2210/pdb8scb/pdb
• EMDBエントリー: 40344
• 分子名称: Ribosomal protein L8, 60S ribosomal protein L11, eL13, ... (92 entities in total)
• 機能のキーワード: termination, sri-41315, ribosome
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 87
• 化学式量合計: 3615287.80

構造登録者

Yip, M.C.J.,Coelho, J.P.L.,Oltion, K.,Tauton, J.,Shao, S. (登録日: 2023-04-05, 公開日: 2023-12-27, 最終更新日: 2024-10-09)

主引用文献

Coelho, J.P.L.,Yip, M.C.J.,Oltion, K.,Taunton, J.,Shao, S.
The eRF1 degrader SRI-41315 acts as a molecular glue at the ribosomal decoding center.
Nat.Chem.Biol., 20:877-884, 2024

PubMed Abstract: Translation termination is an essential cellular process, which is also of therapeutic interest for diseases that manifest from premature stop codons. In eukaryotes, translation termination requires eRF1, which recognizes stop codons, catalyzes the release of nascent proteins from ribosomes and facilitates ribosome recycling. The small molecule SRI-41315 triggers eRF1 degradation and enhances translational readthrough of premature stop codons. However, the mechanism of action of SRI-41315 on eRF1 and translation is not known. Here we report cryo-EM structures showing that SRI-41315 acts as a metal-dependent molecular glue between the N domain of eRF1 responsible for stop codon recognition and the ribosomal subunit interface near the decoding center. Retention of eRF1 on ribosomes by SRI-41315 leads to ribosome collisions, eRF1 ubiquitylation and a higher frequency of translation termination at near-cognate stop codons. Our findings reveal a new mechanism of release factor inhibition and additional implications for pharmacologically targeting eRF1.

PubMed: 38172604
DOI: 10.1038/s41589-023-01521-0

実験手法

ELECTRON MICROSCOPY (2.5 Å)