脂質膜における酵母ATP合成の高解像度冷凍-EM分析
Anurag P Srivastava1, Min Luo2, Wenchang Zhou3
1Department of Biological Chemistry and Molecular Biology, Chicago Medical School, Rosalind Franklin University, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Science (New York, N.Y.)
|April 14, 2018
まとめ
ミトコンドリアのATP合成構造は,そのF0モーターがATP合成をどのように駆動するかを明らかにする. Cryo-EMは 抑制剤であるオリゴミシンが この重要なエネルギー生成プロセスを 阻害することを示しています
科学分野:
- 生物化学
- 構造生物学
- 分子生物物理学
背景:
- mitochondrial adenosine triphosphate (ATP) 合成は,細胞のエネルギー生産を担う重要な酵素複合体である.
- 酵素は,F1サブユニットのATP合成を駆動する,膜に埋め込まれたF0モーターで構成されています.
研究 の 目的:
- 完全なミトコンドリアのATP合成複合体の高解像度構造を決定する.
- オリゴミシンによる陽子の転位と阻害のメカニズムを解明する.
主な方法:
- 単粒子の冷凍電子顕微鏡 (cryo-EM) を使用して酵素を視覚化しました.
- 脂質二層で,抑制剤オリゴミシンと共に,あるいはそれなしに,構造が得られた.
- F6 ステータスサブユニットと δ ローターサブユニットを融合させることで,コンフォーマーションの異質性が減少した.
主要な成果:
- 全ATP合成の高解像度冷凍EM構造 (3. 6と3. 8アングストーム) が得られた.
- F6-δ融合は,ロータの回転とF0c10リングの9°回転を誘導し,ATP合成の方向に整列させた.
- 構造はF1とF0のサブユニットと陽子の転移経路の結合を明らかにします.
結論:
- この研究は,ミトコンドリアのATP合成酵素のメカニズムに関する原子レベルの洞察を提供します.
- この構造は,ATP合成へのタンパク質の流れを 解明する.
- この発見は,ATP合成に対するオリゴマイシンの抑制作用の分子基礎を示しています.
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