展開されたタンパク質は,直接展開されたタンパク質応答を誘導するIre1活性化リガンドです
Brooke M Gardner1, Peter Walter
1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|August 20, 2011
まとめ
展開されたタンパク質応答 (UPR) は,エンドプラズマ網膜 (ER) のタンパク質 Ire1 が展開されたタンパク質に直接結合すると活性化されます. この結合は,特定のアミノ酸残留物によって媒介され,Ire1のオリゴメリゼーションとUPRの活性化を誘発する.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- 展開されたタンパク質応答 (UPR) は,エンドプラズマ網膜 (ER) ホメオスタシスの維持に不可欠な細胞のストレス反応です.
- 超膜タンパク質Ire1は,ERストレスの重要なセンサーであり,その細胞質ドメインをオリゴメライズして活性化することによってUPRを開始します.
- Ire1がERストレスを検出する正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- イーストのIre1タンパク質によるERストレス検出の分子基礎を調査する.
- Ire1.1によって認識される展開されたタンパク質の特性を特定する.
- UPR活性化における直接のタンパク質展開タンパク質相互作用の役割を明らかにする.
主な方法:
- イーストのモデルを使って,Ire1の機能をin vivoで研究した.
- 精製された酵母Ire1コアルメナルドメイン (cLD) を用いてin vitro結合アッセイを行った.
- 様々なアミノ酸組成を用いたペプチド結合特異性を特徴付けました.
- Ire1 cLDの推定ペプチド結合槽に変異を導入し,結合とオリゴメリゼーションを評価した.
主要な成果:
- 酵母Ire1のコアルメナルドメイン (cLD) は,酵母細胞内の展開されたタンパク質に直接結合します.
- Ire1 cLDは,基礎的および水害性残基に富んだペプチドに好ましい結合を in vitroで示す.
- Ire1 cLDの推定ペプチド結合槽内の変異は,ペプチド結合を著しく低下させた.
- Ire1 cLDへのペプチドの結合は,そのオリゴメリゼーションをインビトロで誘導した.
結論:
- Ire1 cLDに展開されたタンパク質の直接結合は,ERストレスを検出する主なメカニズムです.
- Ire1 cLDの結合槽内の特定のアミノ酸残基は,展開されたタンパク質の認識を媒介する.
- この直接的な相互作用とIre1の後のオリゴメリゼーションは,展開されたタンパク質応答の開始に不可欠です.
関連する概念動画
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