大規模なコンフォーメーションダイナミクス制御 H5N1 インフルエンザポリメラーゼ PB2 インポートリンに結合
Elise Delaforge1,2,3, Sigrid Milles1,2,3, Guillaume Bouvignies1,2,3
1Univ. Grenoble Alpes , Institut de Biologie Structurale (IBS), F-38044 Grenoble, France.
Journal of the American Chemical Society
|October 2, 2015
まとめ
インフルエンザPB2タンパク質
科学分野:
- 分子生物学
- ウイルス学
- 構造生物学
背景:
- インフルエンザARNAポリメラーゼ複合体にはPA,PB1,PB2サブユニットが必要です.
- PB2タンパク質は,ポリメラーゼ組成前に核にインポートされます.
- PB2 (627-NLS) のC端は,不明なインポートリン結合機構を持つヘテロダイマーを形成する.
研究 の 目的:
- インプチンに対する627-NLS親和の分子基盤を明らかにする.
- 627-NLSの構造動態を調査する
- 構成の柔軟性が輸入の拘束をいかに促進するかを理解する.
主な方法:
- 溶液状態の核磁気共振 (NMR)
- 小角ニュートロン散乱
- 小角X線散射 (SAXS)
- フォースター共鳴エネルギー伝送 (FRET)
- 化学交換飽和移転 (CEST)
主要な成果:
- 627-NLSは,閉ざされた状態と開いた状態の間の温度依存のダイナミック均衡に存在する.
- 閉じた状態は塩の橋で安定し,開いた状態では破裂する.
- 開いた状態のみがインポートリンαに結合し,形状選択を示唆する.
- インポートインαへの結合は,形状の動的サンプリングを伴う.
結論:
- 627-NLSの固有の形状の柔軟性は,インポートリン結合に不可欠である.
- 温度が機能状態と非機能状態のバランスに影響します
- ダイナミックなアンサンブルからコンフォメーション選択は,効率的な輸入認識を可能にします.
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