特定物种的蛋白质-蛋白质相互作用决定了酵母酵母中的20S蛋白质组的人性化
Sarmin Sultana1, Mudabir Abdullah1, Jianhui Li2
1Centre for Applied Synthetic Biology, Department of Biology, Concordia University, 7141 Sherbrooke St. W, Montreal, QC H3G 1M8, Canada.
Genetics
|June 26, 2023
概括
人类蛋白酶子单元可以取代酵母对应物,揭示关键的蛋白质-蛋白质相互作用 (PPI),对功能至关重要. 特定的相互作用,特别是涉及β2c亚单元.
科学领域:
- 进化生物学是进化的生物学.
- 分子遗传学 分子遗传学
- 保护一些研究研究.
背景情况:
- 酵母和人类共享许多基因,但功能可替换性差异很大.
- 大多数酵母蛋白酶子单元是人性化的,除了核心β环组件,如β2c (HsPSMB7).
研究的目的:
- 开发一种高通量方法,通过创建和选Hsβ2c突变体来使酵母蛋白酶变得人性化.
- 确定特定的蛋白质-蛋白质相互作用 (PPI) 和控制酵母蛋白酶子单元人性化的功能域.
主要方法:
- 产生了大量的人类β2c (HsPSMB7) 突变的图书馆.
- 对补充酵母β2 (ScPup1) 淘汰的选突变物进行了选.
- 分析了影响PPI,蛋白质分解活性和子单元尾巴的变异.
主要成果:
- 通过影响Hsβ2c C端尾相互作用的突变与相邻的β3亚单元实现了补充.
- 与酵母 ScPup1 尾巴交换 Hsβ2c 尾巴,使得它们可以互补.
- 野生类型的人类β2c补充了酵母β2当人类β3被共同表达时.
- 一种催化无活性的HsPSMB7-T44A变体表明了在组装中的作用.
- 人类免疫蛋白酶子单元β2i (HsPSMB10) 不补充酵母β2,表明不同的组装要求.
结论:
- 特定的蛋白质-蛋白质相互作用,特别是在β环核心,对于跨物种的蛋白质酶子单元的功能替代性至关重要.
- β2c的C端尾及其与β3的相互作用是酵母蛋白酶人性化的关键决定因素.
- 在稳定蛋白质酶组合中间体中的蛋白功能需要进一步研究.
- 在构成性和免疫蛋白酶体之间存在组装机制的差异.
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