ABCトランスポーターは,二次活性マルチドラッグトランスロケータドメインを持つ
Henrietta Venter1, Richard A Shilling, Saroj Velamakanni
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Nature
|December 20, 2003
まとめ
研究者らは,二次活性トランスポーターとして機能する,切断された多剤耐性タンパク質 (LmrA) を設計した. これは,一次活性トランスポーターの進化的起源が二次活性系から生じたことを示唆している.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- 多剤耐性 (MDR) は医学における重要な課題であり,しばしば細胞から薬物を排出する活性トランスポーターによって媒介される.
- P-グリコプロテインのようなプライマリ・アクティブ・トランスポーターはATPの水解を用いるが,セカンダリ・アクティブ・トランスポーターはイオン・グラデーションに依存している.
- Lactococcus lactisからのATP結合カセット (ABC) トランスポーターLmrAは,既知の主要な薬物排出ポンプである.
研究 の 目的:
- LmrAの輸送機構におけるATP結合ドメインの機能的役割を調査する.
- LmrAが二次活性トランスポーターとして機能できるかどうかを判断する.
主な方法:
- ATP結合ドメインが欠けている切断されたLmrAタンパク質を設計する.
- 細胞系における断片化されたLmrAの輸送活動を評価する.
主要な成果:
- 断片化されたLmrAタンパク質は,陽子-エチジウムシンポート活性を示した.
- この輸送はATPの水解とは無関係に発生し,二次活性輸送を示しています.
- エンジニアリングされたタンパク質は,多剤吸収システムとして機能した.
結論:
- この発見は,LmrAが二次活性トランスポーターから進化したことを示唆している.
- ATP結合ドメインの獲得により,主活性エフフルスへの移行が可能になった可能性が高い.
- これは,薬物輸送体の進化の経路についての洞察を提供します.
関連する概念動画
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