マルチドラッグトランスポーターの結晶構造は,機能的に回転するメカニズムを明らかにします
Satoshi Murakami1, Ryosuke Nakashima, Eiki Yamashita
1Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan. mura@sanken.osaka-u.ac.jp
Nature
|August 18, 2006
まとめ
TolCとAcrAと作用するEscherichia coliの多剤エフフルストランスポーターAcrBには,大きな結合ポケットがあります. 結晶構造は,オーダーされた基板結合変化による薬物輸出の3段階の回転メカニズムを示しています.
科学分野:
- 微生物学 微生物学とは
- 構造生物学 構造生物学とは
- バイオケミストリー バイオケミストリー
背景:
- AcrBは,Escherichia coli.における重要な多剤流出輸送体である.
- TolC (外膜チャネル) とAcrA (膜融合タンパク質) と連携して機能する.
研究 の 目的:
- AcrB.による多剤輸送の構造的基礎を明らかにする.
- 基板結合と輸出のメカニズムを理解するために.
主な方法:
- X線結晶学を用いて,AcrB.の構造を決定した.
- 構造は,AcrB単独および薬物基板との複合体で得られた.
主要な成果:
- AcrB-薬物複合体は,輸送サイクルにおける異なる機能的状態にある3つのプロトメアを示した.
- サブストラットは,多部位結合を可能にする,大きな芳香的結合ポケットの内部の周回プラズマ領域に位置していました.
- クリスタル構造は,輸送サイクルの異なる構成状態を捕捉した.
結論:
- AcrBは,薬物輸出のための機能的に回転するメカニズムを使用しています.
- 基質の結合と放出は,輸送体内の秩序ある構造変化を伴う.
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