在转录因子Efg1相分离过程中,类域的结构和位置特定的相互作用
Szu-Huan Wang1,2, Tongyin Zheng1,2, Nicolas L Fawzi1
1Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence Rhode Island, 02912, USA.
bioRxiv : the preprint server for biology
|November 21, 2023
概括
在Candida albicans中,Enhanced Filamentous Growth Protein 1 (Efg1) 的类域驱动相位分离,这对于其过渡到致病状态至关重要. 过渡性α螺旋体内的氨酸残留物稳定了这一过程,提供了新的抗真菌点.
科学领域:
- 微生物学和分子生物学
- 生物物理学的生物物理.
- 结构生物学 结构生物学
背景情况:
- 白菌通过表观遗传变化,在开始性和致病性状态之间进行过渡,特别是白色-不透明过渡.
- 这种转换是由转录因子 (TF) 调节的,其中增强的细丝生长蛋白1 (Efg1) 是中心的.
- Efg1的类域 (PrLD) 和相分离能力与此过渡有关,但机制尚不清楚.
研究的目的:
- 为了研究Efg1-介导的相分离的生物物理基础.
- 阐明Efg1的N端 (N) 和C端 (C) PrLDs在这个过程中的作用.
- 确定参与Efg1相分离的关键分子相互作用和残留物.
主要方法:
- 核磁共振 (NMR) 对Efg1 N-PrLD和C-PrLD的结构分析.
- 进行NMR定位实验,研究自身相互作用和RNA结合.
- 凝聚相NMR光谱检测相分离中的氨基酸相互作用.
主要成果:
- Efg1 N-PrLD和C-PrLD在很大程度上是无序的,具有显著的部分α-螺旋结构.
- 在N-PrLD中的部分螺旋结构中介于自我相互作用和RNA结合.
- 在短暂的α螺旋体内,特别是N-PrLD中,氨酸残留物对于稳定Efg1相分离至关重要.
- 过渡的α-螺旋结构在相隔状态下持续存在.
结论:
- 它的PrLDs中的过渡性α-螺旋结构稳定了Efg1相分离.
- 芳香残留物,特别是氨酸,在这种稳定中起着至关重要的作用.
- 了解这些分子机制,可以了解C. albicans的毒性和潜在的针对转录开关的抗真菌策略.
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