機械的に活性化されたイオンチャネルの構造 Piezo1

Kei Saotome^1,2, Swetha E Murthy¹, Jennifer M Kefauver^1,2

¹Howard Hughes Medical Institute, Department of Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.

Nature

|December 21, 2017

まとめ

機械的に活性化されたイオンチャネルの構造を決定し独特のプロペラ形を明らかにし機械的な力に反応して開閉する仕組みを明らかにしました

科学分野:

バイオ物理学
構造生物学
分子生理学

背景:

機械的に活性化されたイオンチャネル,Piezo1とPiezo2は,触覚,自感,および血管の発達に不可欠です.
ピエゾタンパク質の複雑な構造は,ゲートとイオン浸透機構の理解を妨げています.

研究の目的:

マウスPiezo1トリマーの高解像度構造を解明する.
ピエゾ1チャネルの機能と調節を理解するための構造的基礎を提供する.

主な方法:

洗剤で溶解したマウスピエゾ1トリマーの高解像度冷凍電子顕微鏡 (冷凍EM)
細胞外と細胞内領域の構造分析

主要な成果:

ピエゾ1トリマーは独特の3刃のプロペラ構造を採用しています.
構造は,多数のヘリクとピエゾのリピートが柔軟なブレードを形成するカーブされたトランスメブラン領域を明らかにします.
細胞内カーボキシ末端ドメインはイオン孔を形成し,ゲートコンストリクションはサイトゾールに位置する.

結論:

決定された構造は,機械的に活性化されたイオンチャネルであるPiezo1の前例のない原子詳細を提供します.
ピエゾリピートやゲーティングコンストリクションを含む重要な構造要素は,フォースセンシングとアロステリック調節に関する洞察を提供します.
この構造的基盤は,ピエゾチャネルゲートと機械伝導メカニズムに関する将来の研究を促進します.

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