通过PYROXD1介导保护人类tRNA结合酶复合体免受氧化失活化的机制基础
Luuk Loeff1, Alena Kroupova1,2, Igor Asanović3
1Department of Biochemistry, University of Zurich, Zurich, Switzerland.
Nature structural & molecular biology
|March 12, 2025
概括
PYROXD1酶通过与其活性部位结合,保护tRNA结合酶复合体 (tRNA-LC) 免受氧化损伤. 这种由NAD,P) H和FAD调节的相互作用,在有氧条件下维持tRNA-LC功能.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 甲基动物tRNA结合酶复合体 (tRNA-LC) 对于tRNA生物发生和未折叠的蛋白质反应至关重要.
- 它的催化子单元RTCB具有活性部位的氨酸,易受金属离子的氧化失活.
- 氧化还原酶PYROXD1以NAD(P) H依赖的方式保护人类tRNA-LC活性,但机制尚不清楚.
研究的目的:
- 阐明PYROXD1对tRNA结合酶复合体 (tRNA-LC) 氧化失活的保护机制.
- 确定PYROXD1和RTCB之间的相互作用的结构基础.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定人类RTCB-PYROXD1复合物的结构.
- 生物化学试验,以调查NAD,P) H,FAD和甘化在酶活性和保护中的作用.
主要成果:
- 冷-EM结构显示,PYROXD1通过其C端尾部直接与RTCB的催化中心相互作用.
- 结合NAD(P) H和减少FAD的结合对PYROXD1的活性,RTCB的结合和释放进行异质调节.
- PYROXD1的相互作用与阿基酶介导的基化是独有的,这本质上是保护RTCB免受氧化.
结论:
- PYROXD1通过直接与RTCB的活性部位相互作用来保护tRNA-LC活动.
- 这种相互作用通过氧化还原状态和辅因子结合来动态调节.
- 这些发现为如何在有氧条件下维持tRNA-LC活性提供了机械的理解.
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