皮普-霍古:具有协作DNA识别能力的人工组件,能够模仿转录因子对
Zutao Yu1, Chuanxin Guo1, Yulei Wei1
1Department of Chemistry, Graduate School of Science, Kyoto University , Sakyo, Kyoto 606-8502, Japan.
Journal of the American Chemical Society
|February 3, 2018
概括
研究人员开发了可编程的DNA结合剂 (Pip-HoGu),以模仿合作转录因子 (TF) 对,使基因表达的协同破坏成为精确的细胞命运控制.
科学领域:
- 合成生物学
- 分子生物学
- 生物化学
背景情况:
- 合作转录因子对对基因调节至关重要.
- 针对协同TF对-DNA相互作用仍然是一个挑战.
研究的目的:
- 设计一个可编程的DNA绑定系统 (Pip-HoGu),模仿合作TF对-DNA相互作用.
- 评估系统能够协同阻止基因表达的能力.
主要方法:
- 使用环极 (Cyd) -阿达曼坦 (Ada) 合成与宿主 - 客组合 (Pip-HoGu) 结合的烯 - 伊米达聚胺.
- 使用TM,EMSA,竞争性结合,SPR试验和分子动力学进行表征.
- 基于细胞的测试来评估基因表达抑制.
主要成果:
- 皮普-霍古系统形成了稳定,非共价的合作复合体,模仿TF对.
- 该系统展示了可调的识别序列长度和灵活的间隙距离.
- Ada1- Cyd1具有显著的热稳定性和结合亲和力.
- 基于细胞的研究证实了通过破坏TF对DNA功能来强烈抑制基因表达.
结论:
- 模块化Pip-HoGu设计提供了一个模拟合作TF对DNA相互作用的一般框架.
- 这种方法提供了通过向基因调控精确操纵细胞命运的有希望的策略.
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