设db1和Atf7IP形成一个异构三元复合体,阻止了设db1的核出口.
Leena Kariapper1, Ila A Marathe2, Ashley B Niesman3
1Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
bioRxiv : the preprint server for biology
|January 7, 2025
概括
Setdb1和Atf7IP形成了一个稳定的复合体,揭示了Atf7IP是如何调节Setdb1的.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 通过Setdb1的素H3K9甲基化 (H3K9me) 可以使逆转移子 (rTE) 沉默.
- Atf7IP对于Setdb1的核定位,激活和染色质招募至关重要.
- 关于Setdb1/Atf7IP相互作用的结构细节在很大程度上仍然没有被描述.
研究的目的:
- 阐明Setdb1/Atf7IP相互作用的结构基础.
- 了解Atf7IP如何调节Setdb1的核定位和活动.
- 调查Atf7IP对象在Setdb1复合体形成和功能中的作用.
主要方法:
- 用于结构建模的AlphaFold2预测.
- 生物化学复合验证复杂的形成.
- 在体外和细胞内测试以研究蛋白质相互作用.
主要成果:
- 在体外和细胞中,Setdb1和Atf7IP形成了一个稳定的异构三体复合体 (1:2固体测量).
- Atf7IP自我结合,而Setdb1结合可以解决这些多重复合体.
- Atf7IP通过卷轴-卷轴相互作用结合Setdb1,包括Setdb1的核出口信号 (NES),从而防止CRM1介导的核出口.
- 同时,Setdb1与Atf7IP2形成异构分离体,混合异构分离体 (Setdb1/Atf7IP/Atf7IP2) 也是可能的.
结论:
- Atf7IP直接绑定Setdb1的NES动机,抑制核出口并稳定Setdb1在核中.
- 形成具有不同的Atf7IP/Atf7IP2比率的异构体,可以微调Setdb1活性和H3K9me.me.
- 这些发现提供了对Setdb1/Atf7IP复合体对异染色素形成的调节的结构性见解.
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