正確な膜タンパク質のトポゲネシスを開始するにはEMCが必要です
Patrick J Chitwood1, Szymon Juszkiewicz1, Alina Guna1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Cell
|November 13, 2018
まとめ
ER膜タンパク質複合体 (EMC) は,Gタンパク質結合受容体 (GPCR) を含む多くの膜タンパク質の最初の膜域 (TMD) を正しく挿入するのに不可欠です. これは適切なタンパク質の 生成と機能を保証する.
科学分野:
- 分子生物学
- 細胞生物学
- 生物化学
背景:
- 哺乳類は約5,000の統合膜タンパク質を合成する.
- これらのタンパク質がエンドプラズマ網膜 (ER) に挿入されるメカニズムは完全に理解されていません.
- 精密なトポロジック挿入はタンパク質の機能に不可欠です.
研究 の 目的:
- ER膜タンパク質複合体 (EMC) が統合膜タンパク質の生体形成に果たす役割を調査する.
- EMCがタンパク質を ER膜に挿入することを促進する特定のメカニズムを解明する.
- EMCと他のタンパク質転位機構の相互作用を理解する.
主な方法:
- β1 アドレナゲン受容体 (β1AR) バイオゲネシスを用いた再構成試験
- 精製されたEMCとSRP受容体によるin vitro挿入試験
- EMCノックアウト細胞におけるGPCR生殖の分析
- N端のシグナルペプチドを用いたタンパク質トポロジの操作.
主要な成果:
- β1ARと他のGPCRの効率的な生殖には,EMCが必要です.
- EMCは,第1トランスレーションドメイン (TMD1) の挿入に特に必要です.
- EMCなしでは,TMD1の挿入は逆転したり失敗したりしますが,Sec61のトランスロコンは,その後のTMDの挿入を媒介します.
- N端のシグナルペプチドを介してEMC要求を回避すると,EMCノックアウト細胞におけるGPCR生成が回復した.
結論:
- EMCは,膜タンパク質の生殖過程でTMDの正しい同翻訳挿入を保証する上で重要な役割を果たします.
- EMCはSec61トランスロコンと協力して,多数の膜タンパク質の正確なトポゲネシスを達成します.
- EMCの機能を理解することは 膜タンパク質の挿入の複雑なプロセスを解読する鍵です
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