哺乳动物ABC载体P-糖蛋白的能量转导和交替接入
Brandy Verhalen1, Reza Dastvan1, Sundarapandian Thangapandian2
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA.
Nature
|March 15, 2017
概括
这项研究揭示了ATP能量如何通过核酸结合域 (NBD) 的两次循环为P-糖蛋白 (Pgp) 等ABC输送器提供动力. 这种机制驱动了基质流出所必需的形状变化,为PGP运输动力学提供了新的见解.
科学领域:
- 生物化学
- 结构生物学
- 分子生物物理学
背景情况:
- ATP结合盒 (ABC) 输送器利用ATP水解来通过膜移动基质.
- 了解ABC出口国的动态能量传导仍然是一个挑战.
研究的目的:
- 阐明P-糖蛋白 (Pgp/ABCB1) 的ATP和基质结合的结构循环.
- 详细说明ATP能量转导到ABC输送器中的基质转移的机制.
主要方法:
- 使用双电子共振 (DEER) 光谱.
- 使用全原子分子动力学 (MD) 模拟.
- 引入了旋转标签来跟踪形状转变.
主要成果:
- 描述了核酸结合域 (NBD) 中 ATP 能量利用的两次循环.
- 阐明了重构膜域 (TMD) 的形态运动.
- 创建了一个向外面的Pgp形状的原子模型.
结论:
- 通过协调机械和结构数据,为ATP合运输提供了新的视角.
- 在ABC流量传输器类中发现了机械差异.
- 提供了关于PGP在异生菌清除和化疗耐药性中的作用的见解.
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