与NADH结合的AIF通过基质模仿机制激活了线粒体CHCHD4/MIA40的陪伴者
Chris A Brosey1, Runze Shen1, John A Tainer2,3,4
1Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA.
The EMBO journal
|January 13, 2025
概括
诱导亡因子 (AIF) 充当伴侣,使用NADH将CHCHD4等蛋白质在线粒体上. 这一发现揭示了AIF.
科学领域:
- 线粒体生物学 线粒体生物学
- 蛋白质的进口和折叠方式
- 细胞的氧化还原恒温是细胞的氧化还原恒温.
背景情况:
- 线粒体蛋白质的进口依赖于像CHCHD4/MIA40.0.这样的陪伴者.
- CHCHD4和诱导亡因子 (AIF) 之间的相互作用至关重要,但不太了解.
- 双硫化物稳定蛋白质需要在线粒体中进行辅导导入.
研究的目的:
- 阐明CHCHD4-AIF相互作用的结构和机制基础.
- 了解AIF如何监管CHCHD4监护人活动.
- 为了揭示NADH在AIF介导的线粒体进口中的作用.
主要方法:
- 人类CHCHD4的AIF相互作用域的X射线晶体学与激活的AIF二极管.
- 核磁共振 (NMR) 和小角度X射线散射 (SAXS) 溶液测量.
- 突变分析和生物化学测定.
主要成果:
- NADH在全质上配置了AIF以将CHCHD4在线粒体内膜上.
- 该AIF交互域模仿CHCHD4基质识别序列,屏蔽其活动站点.
- 破坏这种屏蔽会增强CHCHD4的基质亲和力和伴侣活性.
- 激活NADH的AIF直接刺激CHCHD4的结合和折叠,通过线粒体进口进行中介.
结论:
- 艾菲是甲二硫化物中继系统的组成部分.
- 激活NADH的二元AIF作为CHCHD4和基质进口的组织中心.
- 艾滋病毒对CHCHD4的调控将细胞NAD (H) 感应与线粒体的氧化酸化能力联系起来.
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