ERADにおけるHrd1リゲーゼトリガースタンパク質のAutoubiquitination
Ryan D Baldridge1, Tom A Rapoport1
1Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Cell
|June 21, 2016
まとめ
研究者は誤った折りたたまれたERタンパク質が 分解のために細胞溶液に移動する方法を調べました 彼らは,Hrd1ユビキチンリガスが ER関連分解 (ERAD) 中の膜にタンパク質を誘導するチャネルを形成している可能性があることを発見した.
科学分野:
- 細胞生物学
- 分子生物学
- 生物化学
背景:
- 誤った折りたたまれたタンパク質は,内プラズマの網膜 (ER) に蓄積される.
- ER関連分解 (ERAD) は,これらのタンパク質を細胞溶液への逆転移とタンパク質分解によって除去する.
- ER膜の逆転移のメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- 誤った折りたたまれた光タンパク質のERAD媒介による逆転移のメカニズムを調査する.
- この過程における Hrd1 ユビキチンリガースの役割を決定する.
- 基質抽出におけるCdc48 ATPaseの機能を明らかにする.
主な方法:
- 浄化されたSaccharomyces cerevisiaeタンパク質を用いたレトロトランスロケーションの復元
- Hrd1ユビキチンリガゼを含むプロテオリポソームを使用した.
- 基質のユビキチン化とHrd1のRING指領域の役割について調査した.
主要な成果:
- 誤った光域の逆転移は,Hrd1の自閉化によって引き起こされる.
- 基板のユビキチネーションはHrd1のオートウビキチネーションの後に行われます.
- Cdc48 ATPaseはレトロトランスロケーションステップ自体には必要ありません.
- Hrd1ライシンのウビキチネーションは,in vitroおよびin vivoのERADにとって不可欠である.
結論:
- Hrd1はレトロトランスロケーションを開始する上で重要な役割を果たします.
- Hrd1はおそらくウビキチンゲート型タンパク質伝達チャネルを形成する.
- このメカニズムは,誤った折りたたまれたタンパク質を ER ルーメンから除去することを容易にする.
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