核酶结合的DNA甲基转移酶DNMT3A和DNMT3B的结构
Ting-Hai Xu1,2, Minmin Liu2, X Edward Zhou1
1Center for Cancer and Cell Biology, Program for Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
Nature
|September 24, 2020
概括
新生DNA甲基转移酶 (DNMT) 3A和3B对于发育和癌症至关重要. 它们与核细胞的相互作用显示了它们如何获取DNA以进行甲基化.
科学领域:
- 表观遗传学
- 分子生物学
- 结构生物学
背景情况:
- DNA甲基化对于哺乳动物的发育和分化至关重要.
- 在癌症中常见的是DNA甲基转移酶 (DNMT) 的失调.
- DNMT3A和DNMT3B优先结合核体,但难以甲基化包裹的DNA.
研究的目的:
- 阐明核子体中新型DNA甲基化的结构机制.
- 了解DNMT3A和DNMT3B如何与核细胞相互作用以访问DNA.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定三元复合体的结构.
- 该复合物包括具有催化能力的DNMT3A2,非活性的DNMT3B3和具有链接DNA的核体核心粒子.
主要成果:
- 结构显示DNMT3B3与核细胞的酸性补丁结合,将DNMT3A2定向到链接DNA.
- 固态约束表明甲基化需要DNA重新定位.
- 这为DNMT偏好链接DNA提供了结构基础.
结论:
- 这项研究揭示了DNMT3A2和DNMT3B3与核细胞相互作用的精确机制.
- 通过正确的酶定位,这种相互作用促进了新的DNA甲基化.
- 了解这一过程对于理解表观遗传调节和癌症发展至关重要.
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