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RyR1のゲート化と活性化のための構造的基礎

Amédée des Georges¹, Oliver B Clarke², Ran Zalk³

¹Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.

|September 24, 2016

まとめ

1型ライオノジン受容体 (RyR1) の構造は,カルシウムとATPの結合が筋肉の収縮を制御する方法を明らかにします. Cryo-EMは RyR1ゲーティングがグローバルとローカルな形状の変化を伴うことを示しチャンネル活性化を説明します

科学分野:

生物化学
構造生物学
分子生理学

背景:

1型ライオノジン受容体 (RyR1) は,細胞内カルシウム放出チャネルである.
RyR1は骨格筋の収縮に不可欠であり,カルシウム動態を調節する.

研究の目的:

RyR1チャネルゲートとアクティベーションの基礎となる構造的メカニズムを解明する.
カルシウム (Ca2+),ATP,カフェインなどの重要な活性化剤の結合部位を特定する.

主な方法:

複数の機能状態における RyR1 の冷凍電子顕微鏡 (cryo-EM) 再構築.
オープンとクローズドのRyR1状態の高解像度構造分析

主要な成果:

特定されたCa2+,ATP,およびカフェインのC端域インターフェースの結合部位.
観察されたCa2+またはATPは,毛穴の膨張なしに"プライミング"の形状変化を誘導する.
RyR1ゲーティングは,S6曲折と毛穴の拡張を含む,グローバルな細胞細胞変化と局所的なトランスメブラン領域の変化を含むことが明らかになった.

結論:

この研究は,RyR1ゲーティングとアクティベーションの詳細な構造的な理解を提供します.
リガンド結合によって誘発されるRyR1の構成の変化は,骨格筋機能にとって極めて重要です.

キーワード:

RYR についてカルシウム放出クリオ・エム刺激収縮カップリングゲーティングライオジン単粒子の再構築構造

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