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誤った折り畳まれたグリコプロテインをERに関連した分解のために選択する光の監視複合体
Vladimir Denic1, Erin M Quan, Jonathan S Weissman
1Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
Cell
|July 29, 2006
まとめ
ER関連分解 (ERAD) 装置は,間違って折りたたまれたタンパク質を特定するために,Yos9p監視複合体を使用します. この複合体は,砂糖の状態をチェックし,ERAD機械に基板を募集することにより,正しいタンパク質分解を保証します.
科学分野:
- 細胞生物学 細胞生物学
- タンパク質の分解
- 分子機構の仕組みについて
背景:
- ER関連分解 (ERAD) 機構が末端に誤折りたたまれたタンパク質を認識する正確なメカニズムはまだ不明です.
- ルーミナルERAD基板の認識は,タンパク質の折りたたみ,グリコシル化状態,およびERレクチンYos9pの影響を受けます.
研究 の 目的:
- ERADマシンの誤折りたたまれたタンパク質の認識におけるYos9pの役割を明らかにする.
- ERADにおけるYos9pを含む複合体の構成と機能を調査する.
主な方法:
- ER内のタンパク質複合体の生化学分析.
- タンパク質の分解経路を評価するための機能検査.
- ERADのコンポーネントを分離するための遺伝子操作.
主要な成果:
- Yos9pは,Hrd1pを含むERADの機械構成要素を備えた安定した複合体の一部であり,ER膜に広がっています.
- Yos9p,Kar2p,Hrd3pは,非原生タンパク質を募集し,糖に依存する分解コミットメントのステップを媒介する光学的監視複合体を形成します.
- Yos9p複合体からHrd1pを分離すると,グリコシル化に無関係な分解が可能になります.
結論:
- Yos9p/Kar2p/Hrd3p複合体は,ERADのゲートキーパーとして機能しています.
- この複合体は,末端に誤折りたたまれたタンパク質をERAD機械に採用することによって,正確な識別を保証します.
- 複合体は基質のグリコシル化状態を調査し,通常の品質管理を回避する不適切な折りたたまれたタンパク質の分解を防止します.
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