哺乳類のABCトランスポーターP-グリコプロテインのエネルギー伝導と交互のアクセス
Brandy Verhalen1, Reza Dastvan1, Sundarapandian Thangapandian2
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA.
Nature
|March 15, 2017
まとめ
この研究では,P-グリコタンパク質 (Pgp) のようなABCトランスポーターに,核酸結合ドメイン (NBD) の2ストロークサイクルでATPエネルギーがどのように供給されるかを明らかにした. このメカニズムは,基質流出に不可欠な形状の変化を駆動し,Pgp輸送ダイナミクスに関する新しい洞察を提供します.
科学分野:
- 生物化学
- 構造生物学
- 分子生物物理学
背景:
- ATP結合カセット (ABC) トランスポーターは,ATPの水解を用いて基質を膜に移動させる.
- ABC輸出国におけるダイナミックなエネルギー伝導を理解することは依然として課題です.
研究 の 目的:
- P-グリコタンパク質 (Pgp/ABCB1) のATPと基板結合型サイクルを解明する.
- ABCトランスポーターの基板へのATPエネルギー伝導のメカニズムを詳細に説明する.
主な方法:
- 二重電子共振 (DEER) スペクトロスコーピーを利用した.
- 全原子分子ダイナミクス (MD) のシミュレーションを使用した.
- 形状の変化を追跡するスピンラベルを導入した.
主要な成果:
- ヌクレオチド結合ドメイン (NBD) での ATP エネルギー利用の2ストロークサイクルについて説明しました.
- トランスメブラン領域 (TMD) を再構成する形状運動を明らかにした.
- 外向きのPgp形状の原子モデルを生成した.
結論:
- 機械的および構造的データを調和させることで,ATP結合輸送に関する新しい視点を提供しました.
- エフフルス・トランスポーター・クラスABCの 機械的な差異を明らかにした.
- 異種生物のクリアランスと化学療法に対する Pgp の役割についての洞察を提供した.
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