K(+) チャンネルにおける活性化ゲートと無活性化ゲートの結合の構造的基礎
Luis G Cuello1, Vishwanath Jogini, D Marien Cortes
1Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.
Nature
|July 9, 2010
まとめ
K (((+) チャンネルの活性化と無活性化の相互作用は,Phe 103のサイドチェーン運動によって機械的に駆動されます. これらの動きは,選択性フィルターを不安定化し,チャネル不活性化を引き起こし,ゲーティング運動に影響を与えます.
科学分野:
- バイオフィジックス 生物物理学
- 構造生物学 構造生物学とは
- 分子生理学 分子生理学
背景:
- カリウム (K(+)) チャンネルは,細胞の電気信号伝達に不可欠です.
- カップリングされた活性化と無活性化ゲーティングは,K (((+) チャンネルの重要な機能特性です.
- 以前の研究では,イオン効果とシステインのアクセシビリティによるカップリングが示されました.
研究 の 目的:
- K(+) チャンネルの活性化と無活性化を結びつける構造的メカニズムを解明する.
- 不活性化を誘発する特定の残留物および移動を特定する.
- KcsAチャネルゲーティングにおけるPhe 103の役割を調査する.
主な方法:
- 様々な開かれた状態の複数のKcsA結晶構造の分析.
- 相互作用エネルギーを計算するための分子動力学シミュレーション.
- サイト指向型変異 (F103A,F103C,F103W) を用いて,機能的効果を評価する.
- シェイカー K (((+)) チャンネル変異体 (I470A) と比較.
主要な成果:
- 内束のゲートの動き,特にTM2ヘリックス回転は,Phe 103を傾けさせる.
- Phe 103の傾きは,孔ヘリックスと隣接する残留物との相互作用によって選択性フィルターを不安定化させます.
- 位置103の変異は,不活性化運動に対するサイズに依存した効果を示しています.
- 分子ダイナミクスは,Phe103と開いた状態の周囲の残留物との間の好ましい相互作用を確認しています.
結論:
- Phe 103 サイドチェーンの再編成は,KcsAにおける機械的にカップルの活性化と無活性化である.
- このメカニズムは,おそらく他のK ((+) チャンネルファミリーにも広がっている.
- アロステリックコップリングは,ステリックコンタクトを通して伝播される機械的変形に依存しています.
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