在PARP15中通过ART域二元化调节ADP-ribosyltransferase活性
Carmen Ebenwaldner1, Antonio Ginés García Saura1, Simon Ekström2
1Division of Biochemistry and Structural Biology, Department of Chemistry, Lund University, Lund, Sweden.
Nature communications
|October 30, 2025
概括
聚ADP-ribose) 聚合酶15 (PARP15) 需要二分化以实现其催化活性,从而影响其在细胞中的功能. 这种二元化机制对于目标参与和蛋白质调节至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 酶学 是一种酶学.
背景情况:
- 聚(ADP-ribose) 聚合酶15 (PARP15) 是一种单-ADP-ribosyltransferase,在抗病毒防御和翻译调节中可能发挥作用.
- 它与PARP14的进化联系和局部化压力颗粒暗示复杂的细胞功能.
研究的目的:
- 研究PARP15的催化机制和调节.
- 阐明二聚化在PARP15活性和细胞局部化中的作用.
主要方法:
- 生物物理技术包括X射线晶体学和-质量谱学 (HDX-MS).
- 在PARP15转移酶域二分化的体外研究.
- 在细胞环境中对全长PARP15的双质破坏性突变的分析.
主要成果:
- PARP15的转移酶域在溶液中二元化,这是其催化活性的先决条件.
- 单质PARP15突变体是不活跃的,而细胞中的二元破坏突变会废除活动并改变局部化.
- 分化促进了目标参与,而不是NAD +共同基质结合,具有独立的原质子功能.
结论:
- 分化是PARP15活动和功能的关键调节机制.
- 这项研究揭示了PARP酶家族中的一种新的调节途径.
- 研究结果提供了关于PARP15在细胞过程中的作用的见解,例如翻译和抗病毒防御.
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