カルシウムで活性化されたTMEM16脂質スクランブラゼのX線構造

Janine D Brunner¹, Novandy K Lim¹, Stephan Schenck¹

¹Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

Nature

|November 11, 2014

まとめ

菌類のTMEM16タンパク質の結晶構造は,カルシウム活性化脂質スクランブラゼとしての機能を明らかにしています. この構造は,TMEM16タンパク質ファミリーの洞察力を提供します.

科学分野:

構造生物学構造生物学とは
メンブラン生物学メンブラン生物学
バイオケミストリーバイオケミストリー

背景:

アノクタミンとも呼ばれるTMEM16タンパク質ファミリーは,カルシウム活性化塩化チャネルと脂質スクランブラゼを含む多様な機能を発揮しています.
TMEM16タンパク質の機能の構造的基礎を理解することは,細胞プロセスにおけるそれらの役割の解明に不可欠です.

研究の目的:

ネクトリア・ヘマトコッカのTMEM16ファミリーメンバーの結晶構造を決定する.
カルシウム活性化リピッドスクランブリングのメカニズムとその関係とTMEM16タンパク質のイオン伝導を調査する.

主な方法:

X線結晶学を用いて,N.ヘマトコッカTMEM16タンパク質の高解像度構造を取得した.
サイト・ディレクテッド・ミュータゲネシスは,保存された残留物の機能とカルシウム結合部位を調査するために使用されました.

主要な成果:

結晶構造は,十のトランスメブランヘリクと,保存されたカルシウム結合部位を含む膜横断腔を持つホモディメルタンパク質を明らかにします.
カルシウム結合部位の突然変異は,真菌のTMEM16タンパク質における脂質スクランブル活性を低下させ,TMEM16A塩化チャネルにおけるイオン伝導に影響を与えた.
この構造は,TMEM16ファミリーの一般的な構造と,そのカルシウム活性化メカニズムを明らかにしています.

結論:

この研究は,カルシウム活性化脂質スクランブラーゼの構造を提示し,TMEM16ファミリー全体のための構造的枠組みを提供します.
この発見は,脂質の乱れとイオン伝導の分子機構の洞察を提供し,TMEM16ファミリー内の保存された機能的要素を強調しています.

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