FicD的TPR域的功能动态是由与ATP和BiP的相互作用调节的
Svenja Runge1, Ecenaz Bilgen2, Andrea Magni3
1Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
概括
人类FicD酶通过可逆连接AMP来调节Hsp70BiP伴侣活性. 这项研究显示FicD
科学领域:
- 分子生物学
- 生物化学
- 结构生物学
背景情况:
- 人类Fic酶FicD调节了内质网中的Hsp70同类BiP.
- FicD通过AMPylation调节BiP活性,降低伴奏功能和基质亲和力.
- 晶体结构表明FicD的四基重复 (TPR) 基因的形状变异性,但动态仍然未知.
研究的目的:
- 研究FicD的TPR图案的形态动态.
- 了解这些动态如何受到ATP和BiP结合的影响.
- 将FicD的动态与其调节功能联系起来.
主要方法:
- 两种颜色,单个分子的福斯特共振能量转移 (smFRET) 实验.
- 动态光子分布分析.
- 进行分子动力学模拟.
主要成果:
- FicD的TPR图案显示了TPR-out和TPR-in状态 (微秒到毫秒) 之间的形态动态.
- 在TPR图案中的标签位置上,形态动态有所变化.
- ATP和BiP结合改变了动态状态的平衡和群体.
结论:
- FicD在其TPR图案中具有显著的形状动态.
- 这些动态与FicD的功能和与BiP的相互作用有关.
- 一个形态景观模型解释了FicD对BiP的动态调节.
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