对于MLL家族甲基转移酶的活性调节的结构基础
Yanjing Li1,2, Jianming Han1,2, Yuebin Zhang3
1National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 333 Haike Road, Shanghai 201210, China.
Nature
|February 18, 2016
概括
研究人员发现RBBP5-ASH2L如何激活MLL蛋白质,这对发育和血液形成中的基因调节至关重要. 这一发现揭示了基因组甲基转移酶调节的普遍机制.
科学领域:
- 生物化学
- 分子生物学
- 表观遗传学
背景情况:
- 混合血统白血病 (MLL) 蛋白家族通过基因组甲基化调节关键的发育和造血基因.
- 已知MLL蛋白活性受到WDR5,RBBP5和ASH2L的刺激,但确切的调节机制尚不清楚.
研究的目的:
- 阐明RBBP5和ASH2L调节MLL家族基因组甲基转移酶的分子机制.
- 了解MLL复合物的组装和活动调节中的共同主题和功能可塑性.
主要方法:
- 对RBBP5-ASH2L异构体进行结构分析.
- 用于确定MLL蛋白激活的生物化学测试.
- 计算机建模以了解激活机制.
主要成果:
- 一个最小的RBBP5-ASH2L异构体作为MLL家族蛋白激活的核心结构单元.
- 一个两步机制解释了MLL蛋白如何被激活.
- 确定了适用于大多数基因组甲基转移酶的通用调节机制.
结论:
- RBBP5-ASH2L异构体对于激活所有MLL家族甲基转移酶至关重要.
- 这项研究揭示了调节基因组甲基转移酶活性的保存机制.
- 这些发现提供了对发育和疾病表观遗传调节的见解.
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