LptB2複合体によるリポポリサッカリド抽出の構造的基礎
Yanyan Li1, Benjamin J Orlando1, Maofu Liao2
1Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Nature
|March 22, 2019
まとめ
グラム陰性細菌にとって不可欠なリポポリサッカリド輸送 (Lpt) 複合体LptB2FGCの構造が明らかになった. LptC について
科学分野:
- 微生物学
- 構造生物学
- 生物化学
背景:
- リポポリサッカリド (LPS) は,グラム陰性細菌の外膜の整合性と抗生物質耐性にとって極めて重要です.
- LptA-Gタンパク質を含むリポポリサッカリド輸送システム (Lpt) は,内側から外側膜へのLPS転移を促進します.
- LptCに関連したATP結合カセットトランスポーターLptB2FGは,内膜からLPSを抽出するための鍵ですが,そのメカニズムとLptCの役割は不明です.
研究 の 目的:
- リポポリサッカリド輸送におけるLptB2FG-LptC複合体 (LptB2FGC) の構造的メカニズムを解明する.
- ATP結合カセットトランスポーターLptB2FGの調節におけるLptCの役割を理解する.
- LptB2FGC複合体とリポポリサッカリドの間の詳細な相互作用を明らかにする.
主な方法:
- LptB2FGとLptB2FGCの構造を決定するために,単粒子の冷凍電子顕微鏡 (cryo-EM) が使用されました.
- 構造は,異なる機能的形状を捕捉するために,ヌクレオチドフリー状態とバナデートトラップ状態の両方で解消されました.
- 凍結EM構造の詳細な分析により,結合したリポポリサッカリドとタンパク質-脂質の相互作用が特定されました.
主要な成果:
- LptB2FGとLptB2FGCの高解像度の冷凍EM構造が,結合したリポポリサッカリドを視覚化して得られた.
- 構造は,トランスポーターとリポポリサッカリドの間の詳細なサイドチェーン相互作用を明らかにし,キャプチャと挤出メカニズムを説明します.
- LptCは,LptB2FG内のトランスメブランヘリックス,ABCトランスポーターのための新しい規制メカニズムを挿入し,LPS輸送を構成変化に結合することが判明しました.
結論:
- LptB2FGCの構造は,細菌の内膜を横断するリポポリサカリド輸送のメカニズムに前例のない洞察を提供します.
- LptCは,LptB2FGの活性を調節し,周辺プラズマのLptタンパク質の相互作用を調整することによって,重要な規制的役割を果たします.
- この複合体の理解は,グラム陰性細菌の抗生物質耐性に対抗する新しい戦略の開発に不可欠です.
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