ATPase 調節されたストレス粒子は,多様なプロテオームとサブ構造を含んでいます

Saumya Jain¹, Joshua R Wheeler¹, Robert W Walters¹

¹Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA.

Cell

|January 19, 2016

まとめ

神経変性疾患に関連したストレス粒子は安定した核構造を持っています ATPが駆動する機械はその組立,動力,そしてコアとシェル構成要素の間の移行を制御します

科学分野:

細胞生物学
神経科学
生物化学

背景:

ストレス粒子は,細胞のストレス条件下で形成されるダイナミックなmRNA-タンパク質複合体です.
これらの粒子は様々な神経変性疾患に関与しており,病理学的関連性を強調しています.
ストレス粒子の組成と調節を理解することは,病気の研究に不可欠です.

研究の目的:

ストレス粒子の構造と分子組成を調べる
ストレス粒子の組立と動態における主要なタンパク質成分とその役割を特定する.
ストレス粒子の振る舞いを調節するATP依存機械の機能を明らかにする.

主な方法:

超高解像度顕微鏡を使ってストレス粒子の構造を可視化しました
精製したストレス・グラニュル・コアを後のタンパク質解析のために.
タンパク質とタンパク質の相互作用と成分を特定するためにプロテオミック分析を行った.

主要な成果:

ストレス粒子の内部の安定したコアサブストラクチャを特定した.
ストレス粒子の内部でタンパク質とタンパク質の相互作用の密集したネットワークを明らかにしました
保存された成分としてATP依存のヘリコースとタンパク質リモデラーを発見した.
ストレス粒子の組立と動態にはATPが不可欠であることを示した.
ATP駆動機械による差異調節が示された:CCTは組み立てを阻害し,MCMとRVBは持続性を促進する.

結論:

ストレス粒子は,ダイナミックな殻に囲まれた安定したコアを特徴としています.
組み立て,分解,そしてコア・シェルの移行は,タンパク質とRNAの改造複合体によって調節されます.
ATPに依存する機械は,ストレス粒子のライフサイクルを調節する上で重要な役割を果たします.
研究結果は,ストレス粒子の形成と病気との関連を明らかにする分子メカニズムを明らかにした.

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