9-1-1检查点的RAD9子单元上的内部和分子间相互作用的结构基础意味着RHINO的功能9-1-1调节
Kodai Hara1, Kensuke Tatsukawa2, Kiho Nagata1
1School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
The Journal of biological chemistry
|February 14, 2024
概括
这种RAD9-RAD1-HUS1 (9-1-1) 复合体调节了DNA损伤检查点. 这项研究揭示了RAD9 C-tail和RHINO蛋白如何与9-1-1环相互作用,影响检查点激活.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 像PCNA和9-1-1复合体这样的真核生物DNA紧件对于DNA交易至关重要.
- 9-1-1复合体,包括RAD9,RAD1和HUS1,激活ATR-CHK1通路用于DNA损伤检查点控制.
- 9-1-1综合体具有环状结构和RAD9 C终端尾部 (RAD9 C尾部),具有调节作用.
研究的目的:
- 在生物化学和结构上分析9-1-1复合体的分子内和分子间相互作用.
- 为了阐明RAD9 C-tail和RHINO蛋白在检查点激活中的调节机制.
主要方法:
- 生物化学测试用于研究蛋白质与蛋白质相互作用.
- 用X射线晶体学确定RHINO. 9-1-1综合体的结构.
- 四级9-1-1-RHINO复合体的结构建模.
主要成果:
- RAD9 C-tail 结合到 9-1-1 环的 RAD9 子单元上的一种疏水口袋.
- 犀牛蛋白与RAD9上相同的疏水口袋结合,表明共享的相互作用地点.
- 晶体结构揭示了RHINO的结合动机,并告知了9-1-1-RHINO四元复合物的模型.
结论:
- RAD9 C尾负面调节9-1-1 DNA结合,而RHINO正面调节检查点激活.
- 在RAD9上的疏水口袋对于分子内 (RAD9 C尾) 和分子间 (RHINO) 相互作用都至关重要.
- 这些发现提供了关于911复合体对DNA损伤检查点的动态调节的见解.
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