通过内在无序的链接器进行双对应相互作用,促进了Notch信号中的转录激活复合体组合
Cyril Cook1, Kristen M Ramsey2, Doug Barrick1
1Thomas C. Jenkins Department of Biophysics, The Johns Hopkins University, Baltimore, MD 21218.
概括
诺奇信号通道的信号通道.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 细胞信号传递 细胞信号传递
背景情况:
- 诺奇信号通路对于细胞分化至关重要.
- 转录是由一个涉及NICD,CSL和MAML的异构三元复合体激活的.
- 涉及两个结合CSL位点的双相对应性对于最大转录激活至关重要.
研究的目的:
- 为了阐明Notch转录激活复合体中双价性的能量.
- 为了确定双价性和异构三聚物形成的能量贡献.
- 分析多价值组件中内在无序的链接器的作用.
主要方法:
- 异热定位热量计 (ITC) 用于确定CSL-ANK-MAML异型的自由能量.
- 为了数据分析,开发了一种强制性异构三聚物模型.
- 对RAMANK的不同区域的约束反应进行了比较,以评估双价性的贡献.
主要成果:
- 通过失调链接器的双性增加了脚林域 (ANK) 的有效度.
- 双价相互作用大约增加了三个数量级的RAM和ANK在CSL结合部位的占用率.
- 对于Notch转录激活复合体组装来说,RAMANK内在无序的链接器至关重要.
结论:
- 双相对应性显著增强了Notch转录激活复合物的组装.
- 内在无序的链接器在高阶的多价值组合中起着关键作用.
- 这项研究提供了一个框架,用于分析复杂构成中内在无序的链接器的能量.
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