vSGLTの結合ポケットからナトリウムと基質の放出のメカニズム
Akira Watanabe1, Seungho Choe, Vincent Chaptal
1Department of Physiology, University of California, Los Angeles, Los Angeles, California 90095-1759, USA.
Nature
|December 7, 2010
まとめ
ナトリウム/ガラクトーゼトランスポーター (vSGLT) は,ナトリウム放出を用いて形状の変化を誘発し,イオンと基板の時間的な放出を保証します. アロステリック経路は,結合輸送のためにナトリウム結合,ヘリックス1および基板結合を結びます.
科学分野:
- 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
- バイオフィジックス 生物物理学
背景:
- 二次活性トランスポーターは,基板輸送のためにイオングラデーションを使用します.
- 5ヘリクスの反転繰り返しのモチーフを持つ膜共輸送タンパク質は,主要な輸送器のクラスです.
- これらのタンパク質におけるイオンと基板輸送の結合メカニズムは不明である.
研究 の 目的:
- Vibrio parahaemolyticus (vSGLT) のナトリウム/ギャラクトーストランスポーターにおけるイオンと基板の結合のメカニズムを解明する.
- vSGLT機能の構造的および動的基礎を調査する.
主な方法:
- 2.7 Åの解像度でvSGLTの内側開いた形状を決定するX線結晶学.
- タンパク質の動力学と構成の変化を分析するための分子動力学シミュレーション.
- トランスポーター機能を評価するための生化学的特徴付け.
主要な成果:
- ナトリウム出口は,トランスメブランヘリックス1の方向転換を誘導し,基板の放出のための内部ゲートを開きます.
- ナトリウム放出は,螺旋状の束の小さな硬体体の動きを誘発し,調整されたイオンと基板の放出を保証します.
- ナトリウム結合部位,トランスメブランヘリックス1と基板結合部位をつなぐアロステル経路が特定され,共輸送結合に不可欠であった.
結論:
- この研究は,vSGLTにおけるナトリウム-ガラクトーザ共同輸送の詳細なメカニズムを明らかにし,ナトリウム放出によって開始された.
- イオン放出によって引き起こされる形状の変化は,基板転移の正確なタイミングを保証します.
- 特定されたアロステル経路は,このトランスポータークラスのイオンと基板輸送の機能的結合に不可欠です.
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