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栄養センサーハブGATOR2の構造
Max L Valenstein1,2, Kacper B Rogala3,4,5,6,7, Pranav V Lalgudi8,9
1Whitehead Institute for Biomedical Research, Cambridge, MA, USA. mvalenst@wi.mit.edu.
Nature
|July 13, 2022
まとめ
栄養素検出とmTORC1の活性化に不可欠なGATOR2複合体は構造的に解明されました. これはケージのような構造と 進化のつながりを明らかにし 細胞の成長の調節に関する 理解を深めるのです
科学分野:
- 細胞生物学
- 構造生物学
- 生物化学
背景:
- ラパミシン複合体1 (mTORC1) のメカニズム的標的は,栄養素への反応として細胞の成長を調節する.
- mTORC1へのアミノ酸シグナルには,Rag GTPases,GATOR1,およびGATOR2が含まれています.
- GATOR2の構造と生化学的機能は,栄養素検出における役割にもかかわらず,以前は知られていなかった.
研究 の 目的:
- 人間のGATOR2複合体の 3次元構造を決定する
- GATOR2のステキオメトリーとアーキテクチャを明らかにする.
- mTORC1経路におけるGATOR2の機能を理解するための構造的基礎を提供する.
主な方法:
- ヒトのGATOR2複合体の構造を決定するために,冷凍電子顕微鏡 (cryo-EM) が使用された.
- GATOR2複合体とその成分について生化学的および構造的分析を行った.
- SEH1LとSEC13のサブユニットの統合は,GATOR2のエスカフォルド内で分析されました.
主要な成果:
- 人間のGATOR2複合体は,二重の対称性を持つ大きな (1.1 MDa) 檻のような構造を形成する.
- 複合体は,WD24,MIOS,およびWDR59のサブユニットで構成された八角形の脚架を備えています. WD40βプロペラで装飾されています.
- SEH1LとSEC13のサブユニットは 骨組みを安定させ 核孔と膜コーティング複合体との進化的つながりを示唆しています
- WD40βプロペラーは,SESN2,CASTOR1,およびGATOR1の栄養センサーとの相互作用を媒介する.
結論:
- この研究は 栄養素検出の重要な要素である GATOR2複合体の完全な構造を明らかにした.
- 決定された構造は,GATOR2のサブユニット組織とその上流規制当局との相互作用に関する洞察を提供します.
- この構造情報は,mTORC1のシグナル伝達と細胞成長制御におけるGATOR2の役割のさらなる調査の基礎となる.
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