素6催化核酶脱酸的结构基础
Zhipeng A Wang1,2, Jonathan W Markert3, Samuel D Whedon1,2
1Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States.
Journal of the American Chemical Society
|March 17, 2023
概括
素6 (Sirt6) 在核细胞上有效地去乙化素H3,而不是自由素. 结构分析显示Sirt6与核细胞DNA和H2A/H2B相互作用,解释了其向的染色体调节.
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染色体结构.
- 赛尔图因是依赖NAD的脱乙酶,影响DNA修复,转录和衰老.
- Sirtuin 6 (Sirt6) 是该家族的一个关键酶.
研究的目的:
- 为了研究Sirt6的基质特异性.
- 阐明Sirt6在核细胞上活动的结构基础.
- 了解Sirt6如何向特定的基因组乙化位点.
主要方法:
- 在Lys9的基因组H3的化学修饰.
- 电子显微镜 (cryo-EM) 的结构分析.
- 对脱乙活性进行生物化学测试.
主要成果:
- Sirt6 能有效地去乙化核素H3 的基因位,但不能去乙化自由基因H3.
- 化EM结构显示了Sirt6与核细胞DNA和H2A/ H2B酸性补丁的相互作用.
- 这些相互作用解释了Sirt6对核体H3位点的偏好和避免H2B乙化.
结论:
- Sirt6 呈现出核细胞特异性脱乙化活性.
- 该结构提供了Sirt6对染色质的向和调节的机制理解.
- 这些发现为了解基因组脱乙酶 (HDAC) 在染色体调节中的作用提供了新的框架.
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