在dynein动力领域的Allosteric通信
Gira Bhabha1, Hui-Chun Cheng1, Nan Zhang1
1Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell
|November 24, 2014
概括
酵母蛋白的AAA1和AAA3 ATPase位点控制微管的运动性. AAA1结合驱动着形状变化,而AAA3则调节这些变化,揭示了运动功能的双重作用.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 丁氨酸是微管基础运输必不可少的运动蛋白质.
- 它们利用环形AAA+ ATPase域进行机械工作.
- 了解单个ATPase位点的精确作用对于阐明dynein功能至关重要.
研究的目的:
- 为了阐明dynein的AAA1和AAA3 ATPase位点在电机的结构变化中的不同作用.
- 为了研究这些部位的核酸结合如何影响机械元素,链接器.
- 揭示了调控dynein的催化循环的调节机制.
主要方法:
- 用X射线晶体学来确定高分辨率结构.
- 电子显微镜 (EM) 用于对dynein复合物的结构分析.
- 生物化学测定和突变研究以探测蛋白质功能.
主要成果:
- 对AAA1的ATP结合会在所有AAA域中引发广泛的形状变化.
- 由AAA1驱动的形状变化导致dynein链接器的显著移动.
- 在AAA3中的核酸过渡作为一个守门员,控制从AAA1到链接器的信号传输.
- 链接器本身在AAA1.1的催化循环中起着调节作用.
结论:
- 迪内因利用不同的ATPase位点 (AAA1和AAA3) 启动和调节运动.
- AAA1是形状变化和链条运动的主要驱动因素.
- AAA3作为一个关键的调节开关,调节形态信号的传播.
- 链接器参与AAA1催化循环的反调节,提供了dynein运动机制的全面视图.
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