反平行EMRE通过在不对称结构之间进行交换来出口药物
Emma A Morrison1, Gregory T DeKoster, Supratik Dutta
1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nature
|December 20, 2011
概括
研究了对抗药性至关重要的大肠杆菌EmrE载体. 我们发现不对称的反平行EmrE单体在向内和向外的状态之间动态交换,解释了功能对称性.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 膜运输 运输 膜运输
背景情况:
- 小型多药性耐药性 (SMR) 载体是理解活性传输机制的关键.
- 来自大肠杆菌的EmrE出口多芳香的阴离子基质,赋予多药性耐药性.
- 埃默尔的同质聚合物拓一直是重要的科学辩论的主题.
研究的目的:
- 阐明 EmrE 传送器的结构动力学和膜拓.
- 为了使EmrE的结构不对称与其活性部位中观察到的功能对称相协调.
主要方法:
- 溶液核磁共振 (NMR) 动力学实验在双细胞中进行.
- 福斯特共振能量转移 (FRET) 来确定单体的方向.
- 偏磁放松增强 (PRE) NMR用于评估水的可访问性.
主要成果:
- 证明了不对称的反平行EmrE单体在向内和向外的构造之间进行交换.
- 量化测量了基质结合的EmrE.的全球形状交换动态.
- 揭示了EmerE二元体内的单体的差异性水可访问性,表明了不对称性.
结论:
- EmrE表现出"动态对称性",其中不对称的单体通过形状交换实现功能对称性.
- 这种动态机制解释了EmrE如何维持运输活动,尽管结构不对称.
- 提供了关于膜蛋白中活性运输的最低要求的新观点.
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