人类SerRS/SIRT2复杂结构揭示了翻译和NAD代谢之间的交叉调节
bioRxiv : the preprint server for biology
|October 3, 2025
概括
一项新的研究揭示了代谢和翻译是如何联系在一起的. 酶血-tRNA合成酶 (SerRS) 通过ADP-ribose与sirtuin-2 (SIRT2) 相互作用,调节蛋白质合成并可能在压力期间保护细胞.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 细胞过程需要复杂的协调.
- 代谢和翻译是细胞的基本活动.
- 调节翻译对于细胞功能至关重要.
研究的目的:
- 阐明细胞代谢和转化之间的交叉调节.
- 为了确定人体细胞质血清-tRNA合成酶 (SerRS) 和sirtuin-2 (SIRT2) 之间的相互作用的结构基础.
主要方法:
- 3.2 用冷电子显微镜 (cryo-EM) 确定与SIRT2结合的SerRS的结构.
- 生物化学测试,以评估相互作用对tRNA结合和蛋白质合成的影响.
主要成果:
- 一个新的冷EM结构揭示了SerRS与SIRT2结合,由ADP-ribose (ADPR) 调节.
- 这种相互作用阻断了SIRT2的活性部位,并且在固态/全固态上阻碍了tRNA与SerRS.结合.
- 这种结合降低了充电的tRNA水平和蛋白质合成活性,独立于SerRS乙化.
- 相互作用的残留物的共同进化表明了一个保存的调节机制.
结论:
- 由ADPR诱导的SerRS/SIRT2相互作用代表了新型的新陈代谢和翻译之间的交叉调节.
- 这种相互作用可能起到细胞保护机制的作用,尤其是在ADPR积累的压力条件下.
- 这些发现提供了关于细胞应激反应和蛋白质合成代谢调节的见解.
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