在组装Wnt增强酶体时,BCL9-Pygo和LDB-SSBP复合体之间的相互作用的结构基础
Hongyang Wang1, Mariann Bienz2, Xiao-Xue Yan3
1School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Nature communications
|June 22, 2023
概括
在Wnt增强一些osome.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 结构生物学 结构生物学
背景情况:
- 该Wnt增强酶体调节Wnt响应基因,是癌症治疗点.
- 了解 Wnt enhanceosome 组合至关重要,但人们对其了解甚少.
研究的目的:
- 阐明 Wnt 增强酶组合背后的分子机制.
- 为了确定关键的蛋白相互作用和Wnt增强osome核心复合物的结构特征.
主要方法:
- 同免疫沉测试以确定蛋白质复合体的形成.
- 一个三元复合体的晶体结构的确定 (Pygo2,LDB1,SSBP2).
- 在基因淘汰的人类细胞系中的功能分析.
主要成果:
- BCL9,Pygo,LDB1和SSBP形成了一个稳定的核心复合体.
- 在Pygo的N端NPF基因中介于与LDB1-SSBP核心的结合.
- 晶体结构显示 LDB1-SSBP2 通过 NPF 基因与两个 Pygo2 分子结合.
- 这种相互作用对于Wnt/β-catenin依赖转录至关重要.
结论:
- BCL9-Pygo-LDB1-SSBP复合体形成了Wnt增强酶体的稳定核心.
- 皮戈的NPF图案对于复杂的组装和功能至关重要.
- LDB1-SSBP2结合槽代表了Wnt信号抑制的潜在药物标.
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