异构ABC输出器中大规模形态转换的原子化机制
Hendrik Göddeke1, M Hadi Timachi2, Cedric A J Hutter3
1Theoretical Chemistry, Faculty of Chemistry and Biochemistry , Ruhr-University Bochum , 44780 Bochum , Germany.
Journal of the American Chemical Society
|March 17, 2018
概括
这项研究揭示了ATP结合盒 (ABC) TM287/288的原子机制. 它展示了ATP结合如何驱动构造变化,通过一个封闭的中间体将传送器从面向内向面向外的状态.
科学领域:
- 结构生物学
- 生物化学
- 分子生物物理学
背景情况:
- 酸结合盒 (ABC) 运输器使用酸结合和水解进行基质转移.
- 核酸结合域 (NBD) 和跨膜域 (TMD) 之间的动态合仍然不太清楚.
- 了解这些动态对于阐明膜运输机制至关重要.
研究的目的:
- 阐明在ABC出口者TM287/288中构造转换的原子层次机制.
- 在原子分辨率上描述封闭和面向外的状态.
- 在运输周期中研究NBD和TMD运动之间的合.
主要方法:
- 全原子分子动力学 (MD) 模拟.
- 电子磁共振 (EPR) 光谱学
- 在多个微秒内在明确的膜/水环境中进行模拟.
主要成果:
- 在ATP结合时,TM287/288通过一个封闭的中间体从向内 (IF) 转向向外 (OF) 状态.
- ATP结合会诱导NBD二分体的收紧和细胞内TMD门的关闭,形成Occ状态.
- 随后的细胞外TMD门开放导致OF状态,门永远不会同时开放.
结论:
- 提出了TM287/288形态循环的详细原子机制.
- 通过协调域和TMD内部的形状变化实现NBD-TMD合.
- 这项研究提供了对异构ABC出口商的功能性工作周期的原子层面见解.
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