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组合性希斯基因修改对ATAD2和ATAD2B基因对乙氨酸识别的影响
Margaret Phillips1,2, Kiera L Malone1, Brian W Boyle1
1Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, Vermont 05405, United States.
Journal of medicinal chemistry
|May 11, 2024
概括
含有2 (ATAD2) 和ATAD2B蛋白质的ATPase家族AAA+域具有能够读取基因组修饰的体. ATAD2B基因组与ATAD2基因组不同,它与其他标记结合了乙化基因组.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 含有2 (ATAD2) 的ATPase家族AAA+域及其对应物ATAD2B蛋白质是表观遗传调节剂.
- 它们的C端基因组 (C-terminal bromodomains,简称BRD) 识别了基因组蛋白上的乙化氨酸残留物,从而影响了基因表达.
研究的目的:
- 调查ATAD2和ATAD2B基因对乙化氨酸残留物的结合选择性.
- 为了了解邻近的基因组后翻译修改如何影响这种识别.
- 为了阐明ATAD2/Bodomain-histone相互作用背后的结构机制.
主要方法:
- ATAD2和ATAD2B类动物的结构功能分析.
- 生物化学测试以评估与改性质素的结合.
- 进行X射线晶体学,以确定原体-连接体复合体的结构.
主要成果:
- ATAD2B 基体表现出更广泛的结合,容纳具有相邻甲基化或酸化标记的乙化组素配体.
- ATAD2基因的乙氨酸结合因相邻的修改而显著受损.
- 结构数据显示,在结合口袋内的ATAD2/B BRD残留物,受到邻近标记的影响,对乙氨酸的特定协调.
结论:
- 多种组织组织蛋白修饰的相互作用决定了ATAD2/Bodomains的结合特异性和结合方式.
- 这种差异性识别表明,ATAD2和ATAD2B在解释基质子代码方面有不同的作用.
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