J-タンパク質のコチャペロンは,BIPをIRE1をモノメリ化し,展開されたタンパク質反応を抑制する
Niko Amin-Wetzel1, Reuben A Saunders1, Maarten J Kamphuis1
1Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
Cell
|December 5, 2017
まとめ
展開されたタンパク質応答 (UPR) は,IRE1の活性化を抑制するコチャペロンであるERdj4によって制御されます. 解き放たれたタンパク質は,この抑制を妨害し,UPR信号を活性化し,内プラズマ網膜の恒常性を回復させます.
科学分野:
- 細胞生物学
- 分子生物学
- 生物化学
背景:
- タンパク質の折りたたみ反応 (UPR) を通して,タンパク質折りたたみホメオスタシスを維持する.
- UPRシグナリングは,展開されたタンパク質に反応して,トランスメブランERストレス受容体であるIRE1のオリゴメリゼーションによって開始されます.
- ERのストレスを IRE1の活性化に結びつける正確なメカニズムは不明である.
研究 の 目的:
- ERdj4/DNAJB9が,UPR中のIRE1の活性化を調節する役割を明らかにする.
- ERdj4 と BiP と IRE1 の間の相互作用を,ERストレスの反応として調査する.
主な方法:
- タンパク質複合体の形成を研究する in vitro 生化学試験
- IRE1 オリゴメリゼーションとアクティベーションの分析
- UPR規制におけるBiPとJドメインのコチャペロンの役割を調査する.
主要な成果:
- ERdj4は,光のHsp70 BiPとIRE1の光域 (IRE1 ^ LD) と複合体を形成することによって,IRE1の選択的抑制剤として作用する.
- ERdj4は,BIPとIRE1^LDの結合を容易にし,ATPの水解を刺激し,IRE1ジメルを破壊する.
- 展開されたタンパク質の蓄積はBiPを移動させ,IRE1 ^ LDが二重化し,UPRシグナリングを活性化する.
結論:
- ERdj4を含むBiPとJドメインのコチャペロンは,UPRの重要なレギュレーターです.
- ERdj4によるIRE1抑制は,ERにおけるタンパク質折り畳みのホメオスタシスの維持に重要なステップである.
- これらの調節メカニズムを理解することで 細胞のストレス反応の洞察が得られます
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