硫素-氧素复合体的结构揭示了一个基本的修复拥抱
Thomas J Jönsson1, Lynnette C Johnson, W Todd Lowther
1Center for Structural Biology and Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Nature
|January 4, 2008
概括
硫化素 (Srx) 通过展开其C端,揭示活性位点来修复过氧化过氧化素 (Prx). 这种对恢复过氧化酶活性至关重要的相互作用,为蛋白质结合和细胞信号调节提供了洞察力.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 2-Cys过氧化 (Prxs) 调节过氧化信号传递.
- Prx无活化是通过活性位点cysteine的过氧化到cysteine硫酸发生的.
- 硫化素 (Srx) 修复过氧化Prx,恢复过氧化酶活性并终止信号.
研究的目的:
- 阐明Srx访问和修复高氧化Prx活性部位的结构机制.
- 了解Srx和PrxI之间相互作用的结构基础.
- 研究特定蛋白质与蛋白质相互作用在修复机制中的作用.
主要方法:
- 人体Srx-PrxI复合体在2.6A分辨率上的X射线晶体学.
- 使用位点定向突变体的结合性研究和活动分析.
- 蛋白质-蛋白质接口和活性部位重排的结构分析.
主要成果:
- 晶体结构揭示了Prx C端的完整展开,该端与Srx的背面结合.
- 这种相互作用接口对于修复过氧化Prx.是必不可少的.
- 在Prx中,活性位点的重新排列与Srx的ATP结合位点对应,解释了最初的催化步骤.
结论:
- Srx-PrxI复合结构为Srx进入埋藏的硫酸部分提供了一种机制.
- 识别的交互接口对于Srx介导的Prx修复和信号终止至关重要.
- 这些发现表明,与Prxs.交互的其他蛋白质的结合模式是保留的.
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