酸盐依赖的核出口通过一种新的NES类通过MSn5出口得到认可
bioRxiv : the preprint server for biology
|August 30, 2024
概括
酵母出口 Msn5 在转录因子 Pho4.4 上识别了一种新的化核出口信号 (NES). 这种酸特异性相互作用和 Msn5 自抑制揭示了核运输调节的新机制.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 信号蛋白的核运输对于基因表达调节至关重要.
- 信号蛋白的酸化通常决定了它们的亚细胞定位和功能.
- Msn5中的酵母出口中介于核出口,但其货物识别机制尚未完全理解.
研究的目的:
- 为了阐明出口酵母Msn5及其货物之间的相互作用的结构基础,酸盐感应转录因子Pho4.
- 揭示4酸化调节其核出口的机制.
- 调查Msn5的自身抑制机制及其对货物结合的影响.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定与Pho4.4结合的Msn5的结构.
- 生物化学试验用于研究蛋白质-蛋白质相互作用和结合动力学.
- 现场定向突变发生,探讨特定残留物在结合和出口中的作用.
主要成果:
- Pho4使用一种新的,扩展化35残留核出口信号 (NES),它与Msn5.5的面结合.
- 在Pho4中,两种酸化血清残留物直接与Msn5上的基本贴片相互作用,调解酸盐特异性识别.
- 未结合的Msn5是自抑制的,而Pho4结合,以及Ran结合,克服了这种抑制,促进Pho4在细胞质中释放.
结论:
- 这项研究揭示了以前未知的核运输中酸盐特异性识别机制,该机制由一种新的NES介导.
- Msn5的自身抑制机制解释了货物绑定和释放的合作性,为受管制的核出口提供了洞察力.
- 这些发现扩大了对各种核出口信号的理解,以及货物酸化在蜂信号传输中的关键作用.
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