COMPASS H3K4甲基转移酶复合体的结构和形态动力学
Qianhui Qu1, Yoh-Hei Takahashi2, Yidai Yang3
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|August 14, 2018
概括
lysine 4 (H3K4) 的基因组甲基化受 COMPASS 综合体的调节. 低温电子显微镜揭示了酵母Set1/COMPASS的核心结构,详细描述了其催化活性至关重要的蛋白相互作用.
科学领域:
- 生物化学
- 分子生物学
- 结构生物学
背景情况:
- 基因组3素4 (H3K4) 甲基化是一种关键的表观遗传修饰.
- 这一过程是由进化保存的COMPASS (与Set1相关的蛋白质复合体) 甲基转移酶家族介导的.
- COMPASS 活动依赖于各种物种,包括酵母和人类共享的核心蛋白质.
研究的目的:
- 阐明酵母SET1/COMPASS核心复合物的结构组织和动态.
- 提供有关COMPASS功能的原子层面见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得酵母Set1/COMPASS核心复合物的高分辨率图.
- 结构分析的重点是解决核心COMPASS蛋白的排列和相互作用.
主要成果:
- 酵母Set1/COMPASS核心复合物的冷电磁图得到了4.0至4.4Å的分辨率.
- Cps50 C端尾作为一个中心支架,促进复杂的组装.
- 催化SET域位于复合体的结点,与Cps60,Cps50和Cps30进行广泛的相互作用.
- SET 域的 SET-I 基因被 Cps30 参与,解释了它在较高 H3K4 甲基化状态中的作用.
结论:
- 该研究提供了酵母Set1/COMPASS核心复合物的高分辨率结构模型.
- 详细的结构洞察力揭示了核心蛋白质如何促进复合体的稳定性和催化功能.
- 了解COMPASS结构是解读基因表达的表观遗传调节的关键.
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