通过SAGA DUB模块进行素H2B脱的结构基础
Michael T Morgan1, Mahmood Haj-Yahya2, Alison E Ringel1
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
概括
在Spt-Ada-Gcn5乙转移酶 (SAGA) 脱化 (DUB) 模块
科学领域:
- 表观遗传学
- 分子生物学
- 结构生物学
背景情况:
- 在转录激活过程中,单基酸素H2B至关重要.
- 该Spt-Ada-Gcn5乙转移酶 (SAGA) 协同激活器复合体包括一个负责H2B去除的二化 (DUB) 模块.
- 了解DUB模块与组织蛋白的相互作用是解读转录调节的关键.
研究的目的:
- 阐明SAGA DUB模块与无处不在的基因子相互作用的结构基础.
- 调查 DUB 模块对 H2B 基因组进行脱的机制.
- 确定这些相互作用对转录过程的影响.
主要方法:
- 用X射线结晶学来确定DUB模块与无处不在的核素相结合的结构.
- 生物化学测定以评估不同环境中的脱活动.
- 对DUB模块,基因组和基因组辅助体之间的蛋白质-蛋白质相互作用进行分析.
主要成果:
- 晶体结构显示了DUB模块和H2A/H2B酸性补丁之间的特定接触,由Sgf11上的氨酸集群介导.
- 催化域Ubp8与H2B和附加的ubiquitin进行相互作用.
- DUB模块有效地在核体和H2A/H2B二聚体形式中解H2B,包括与FACT伴侣相关的形式.
结论:
- SAGA DUB 模块使用精确的结构机制来识别和结合无处不在的 H2B 在核体上.
- 在不同的基因组环境中保持脱化活性,这表明它在动态核体重塑中的作用.
- SAGA 的 DUB 模块可能会在核细胞转换的多个阶段中准 H2B,从而影响转录调节.
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