通过Rtt109对Histon H3 K56的Asf1依赖性乙化进行多位基质识别
Lin Zhang1, Albert Serra-Cardona2, Hui Zhou2
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, 100049 Beijing, China.
Cell
|July 31, 2018
概括
这种酶对DNA复制和基因组稳定性至关重要. 它的活性需要由晶体结构分析揭示的基因素A1和基因素H3和H4的特定结构变化.
科学领域:
- 生物化学
- 分子生物学
- 表观遗传学
背景情况:
- 基因乙化调节基因表达和DNA修复.
- 基因组组合和基因组稳定性至关重要的基因组组合是H3 lysine 56 (H3K56) 的Rtt109.
- 对Rtt109的活性至关重要,但底层机制尚不清楚.
研究的目的:
- 阐明Rtt109和Asf1合作以乙化H3K56的结构机制.
- 了解H3K56乙化的基质识别过程.
主要方法:
- 用X射线结晶学来确定Rtt109-Asf1-H3-H4复合物的结构.
- 生物化学试验分析结构发现的功能后果.
主要成果:
- 晶体结构显示,Asf1解开了基因组H3的N端α螺旋并稳定了基因组H4的C端β链,这是H3K56乙化的先决条件.
- 也需要在Rtt109和基因素H3的中心螺旋之间发生意想不到的相互作用.
- 这些发现表明了复杂的多站点基质识别机制.
结论:
- 这项研究提供了对H3K56乙化中的Rtt109和Asf1功能的机制理解.
- 这些发现为基质修饰酶的基质识别提供了一般的见解.
- 这项研究阐明了基因组监护体和特定基因组结构在表观遗传调节中的作用.
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