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通过冷EM揭示了与DNMT1结合的活性和非活性状态中USP7的结构

Nao Nakamura¹, Sae Yoshimi¹, Amika Kikuchi¹

¹Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Kanagawa, Japan.

Structure (London, England : 1993)

|July 11, 2025

概括

无处不在特异性蛋白酶7 (USP7) 被DNA甲基转移酶1 (DNMT1) 激活,以维持DNA甲基化. 在结合DNMT1时,USP7从无活跃状态转变为活跃状态,从而使素H3的二维基化成为可能.

科学领域:

表观遗传学和基因调控
分子生物学分子生物学
生物化学生物化学

背景情况:

维护DNA甲基化对于细胞过程至关重要.
UHRF1通过基因组H3的无处置,将DNA甲基转移酶1 (DNMT1) 引入半甲基化DNA中.
乌比奎特异性蛋白酶7 (USP7) 与DNMT1相互作用,将乌比奎从基因素H3.3中去除.

研究的目的:

在DNMT1结合的背景下阐明USP7的激活机制.
为了了解USP7如何在DNMT1的RFTS域被绑定时对H3基因组分离.

主要方法:

生物化学测定生物化学测定
结构研究结构研究
低温电子显微镜 (cryo-EM) 单颗粒分析

主要成果:

当USP7与DNMT1RFTS域结合时,对无处不在的H3是不活跃的.
当USP7与DNMT1.1复杂化时,有效地使无所不在的H3脱.
低温电磁探测揭示了USP7在结合DNMT1时经历了形状转变 (开放到关闭),与激活相关.

结论:

通过DNMT1结合,USP7通过一种形状变化被激活.
这种激活机制是DNA甲基化维护中的二维基化过程的关键.

关键词:

通过DNA甲基化.在 DNMT1 中,DNMT1 的值是:USP7 USP7 美国低温电磁波冷却器 (Cryo-EM) 是一个非常好的方法.无处不在/去无处不在

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