UFM1 E3リガゼは,ERから60Sリボソームサブユニットのリサイクルを促進します
Paul A DaRosa1, Ivan Penchev2, Samantha C Gumbin1
1Department of Biology, Stanford University, Stanford, CA, USA.
Nature
|February 21, 2024
まとめ
ユビキチンとユビキチンのようなタンパク質 (UBL) は細胞の行動を調節する. この研究は,UFM1リガスがリボソームタンパク質L24を改変し,ER膜から60Sサブユニットの救済とリサイクルを助ける方法を示しています.
科学分野:
- 分子生物学
- 細胞生物学
- 構造生物学
背景:
- ウビキチンおよびウビキチン類似タンパク質 (UBL) は,タンパク質を逆転的に改変することによって,重要な細胞プロセスを媒介する.
- UFM1は主にER関連リボソームのリボソームタンパク質L24を修正し,60Sサブユニット救済を支援します.
- UFM1のターゲット選択の正確なメカニズムと60S救出におけるその役割は不明でした.
研究 の 目的:
- リボソーム UFMylation の分子メカニズムを UFM1 E3 リガゼ (E3 ((UFM1)) によって解明する.
- E3 ((UFM1) 基質認識とL24へのUFM1転送の構造的基礎を決定する.
- 大型リボソームサブユニットの終結後の放出とリサイクルにおけるE3 (UFM1) の役割を調査する.
主な方法:
- クリオ電子顕微鏡 (cryo-EM) で,その基板と相互作用するE3の連続的なスナップショットをキャプチャします.
- UFMylation装置の機能と相互作用を評価するための生化学分析.
- 自由な60SサブユニットでリボソームUFMylationを観察するためのインビボ試験.
主要な成果:
- リボソームUFMylationは, in vivoで自由の60Sサブユニットで発生する.
- Cryo-EM構造は,L1茎とtRNA結合部位にE3 ((UFM1) を結合し,L24を150 Å 以上の距離で変異させる.
- E3 ((UFM1) は,UFMylated 60Sサブユニットの周りに安定したC形クランプを形成します.
結論:
- E3 ((UFM1) は,60SサブユニットでL24の精密な修正を達成するためにユニークなメカニズムを使用します.
- E3 (UFM1) -UFMylated 60S複合体は,大リボソームサブユニットのER膜からの放出とリサイクルを促進する.
- この研究は,リボソーム品質管理とタンパク質合成の規制に関する構造的な洞察を提供します.
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