不对称的形状和脂质相互作用塑造了异构体ABC载体的ATP合循环
Qingyu Tang1, Matt Sinclair2, Hale S Hasdemir2
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Nature communications
|November 8, 2023
概括
这项研究揭示了BmrCD多药物出口者如何改变形状以运输分子,使用冷电子显微镜 (cryo-EM) 和模拟. 基质和脂质的不对称结合驱动了这种由ATP驱动的运输机制.
科学领域:
- 结构生物学 结构生物学
- 生物化学 生物化学
- 分子生物物理学 分子生物物理学
背景情况:
- ATP结合盒 (ABC) 载体是关键的膜蛋白,参与多药性耐药性.
- 了解ABC载体的结构动态是开发新治疗策略的关键.
研究的目的:
- 阐明异构体ABC多药出口者BmrCD的结构和动态机制.
- 描述BmrCD.的ATP和基质结合的向内转向 (IF) 和封闭 (OC) 状态.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于高分辨率的结构确定.
- 双电子电子共振光谱 (DEER) 用于距离测量.
- 分子动力学 (MD) 模拟来分析形状变化和脂质相互作用.
主要成果:
- 在IF和OC状态下确定了BmrCD的结构,揭示了ATP结合时亚单元对称性的变化.
- 观察到不对称的基质和Mg2+结合,可能调节ATP水解.
- 证明了与IF和OC形状的差异性脂质结合,调节载体的能量格局.
结论:
- 不对称的形状在BmrCD的ATP合运输机制中起着至关重要的作用.
- 脂质相互作用是调节能量格局和ABC载体的功能不可或缺的一部分.
- 这些发现为ABC超级家族蛋白质中依赖ATP的运输的一般机制提供了见解.
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