无序的时钟蛋白相互作用和充电块将一个沙钟变成了一个持续的昼夜振荡器
Meaghan S Jankowski1, Daniel Griffith2, Divya G Shastry1
1Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
Nature communications
|April 25, 2024
概括
昼夜时钟蛋白中的无序区域,如FRQ,对于相互作用至关重要. 这项研究表明,FRQ中的正电荷块对于时钟定时和生理输出至关重要.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 生物化学 生物化学
背景情况:
- 循环时钟通过蛋白质复合体的反循环来调节生理过程.
- 时钟蛋白中的内在无序区域 (IDR) 调解相互作用,但它们的具体作用尚不清楚.
- 神经体中FRQ蛋白是真菌昼夜钟的关键组成部分.
研究的目的:
- 调查内在无序区域在昼夜钟蛋白相互作用中的功能作用.
- 在FRQ中识别特定的残留物和分子特征,这些残留物和分子特征与其合作伙伴FRH.中介相互作用.
- 了解这些相互作用对昼夜时钟功能和输出的贡献.
主要方法:
- 对无序时钟蛋白FRQ的合成微阵列分析.
- 现场定向突变发生,以改变FRQ中的特定残留物和充电块.
- 评估FRH与FRQ结合的情况.
- 对响应FRQ突变的时钟振荡和生理输出进行分析.
主要成果:
- 在FRQ中确定了关键的残留物,这些残留物对于与FRH相互作用至关重要.
- 证明FRH对于持续的时钟振荡是必要的,但不是转录抑制.
- 发现一种富含的FRH与负电荷的FRQ结合,特别是在残留物的"块"中.
- 表明,在FRQ中删除正电荷块会破坏核心时钟定时和生理输出.
- 在压制性昼夜钟蛋白中发现的正电荷集群是常见的.
结论:
- 内在无序的区域,特别是FRQ中的正电荷块,在昼夜时钟的功能中起着机械作用.
- 这些带正电荷的区域对于调节核心时钟定时和生理输出的介导相互作用至关重要.
- 这些发现提供了关于压制臂蛋白在生理时钟机制中的功能的见解.
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