对Yap1转录因子局部化的氧化还原调节的结构基础
Matthew J Wood1, Gisela Storz, Nico Tjandra
1Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.
Nature
|August 20, 2004
概括
在氧化应激过程中,Yap1转录因子控制基因表达. 它的结构通过二硫化物键发生变化,调节其在核和细胞质之间运动.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 生物必须适应基因表达环境变化,以求生存.
- 在Saccharomyces cerevisiae中,Yap1转录因子是控制氧化应激反应的关键.
- 激活的Yap1移动到细胞核,影响多达70个基因.
研究的目的:
- 在Yap1.1.中识别一个氧化还原调节的域.
- 为了确定这个域的高分辨率解决方案结构.
- 为了阐明Yap1的亚细胞局部化控制的机制.
主要方法:
- 结构生物学技术来确定Yap1的溶液结构.
- 生物化学试验,以调查氧化还原依赖相互作用.
- 位点定向突变发生以探测功能域.
主要成果:
- 在Yap1中发现了一个氧化还原调节的域,并进行了结构性特征.
- 在氧化状态下,Yap1的核出口信号 (NES) 被二硫化物键掩盖.
- 水相互作用的破坏阻止了氧化还原调节的局部化变化.
- 减少二硫化物键导致非结构化的构造,暴露了NES,并允许细胞质再分配.
结论:
- 这项研究揭示了氧化还原依赖Yap1局部化的结构基础.
- 介绍了一种通过可逆二硫化物键调节转录因子的新机制.
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