结构动力学分析USP14通过AKT介导酸化激活的结构动力学分析
Raju Dash1, Non-Nuoc Tran1, Sung Bae Lee2
1Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
Cells
|June 19, 2024
概括
通过诱导结构变化,AKT酸化激活了Ubiquitin特异蛋白酶14 (USP14). 这种酸化增强了USP14的作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 乌比奎特异性蛋白酶14 (USP14) 是一种与蛋白质组相关的关键双化酶 (DUB).
- 众所周知,Ser432的AKT介导酸化激活USP14,通过ubiquitin-proteasome系统 (UPS) 影响全球蛋白质降解.
研究的目的:
- 为了阐明通过AKT酸化激活USP14的原子级分子机制.
- 描述USP14在酸化后的结构动态变化.
主要方法:
- 对USP14催化域进行了分子动力学 (MD) 模拟,其处于非活性,活性和USP14-ubiquitin复合体状态.
主要成果:
- 酸化Ser432诱导了USP14的阻断循环 (BL) 中显著的构造变化,使其从开放循环转变为β-sheet结构,这对激活至关重要.
- 酸化增加了USP14和ubiquitin之间必要的结合和盐桥相互作用的频率,增强了deubiquitinating活性.
结论:
- 在Ser432的酸化在调节USP14的局部 conformational 景观和活动中起着至关重要的作用.
- 这些发现为USP14介导的蛋白酶体调节和潜在的治疗点设计提供了洞察力.
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