在Frizzleds中,路径选择性是通过保存的微开关来实现的,这些微开关定义了路径决定性,活跃的构造
Lukas Grätz1, Maria Kowalski-Jahn1, Magdalena M Scharf1
1Karolinska Institutet, Dept. Physiology & Pharmacology, Sec. Receptor Biology & Signaling, Biomedicum, S-17165, Stockholm, Sweden.
Nature communications
|July 29, 2023
概括
的受体 (FZD) 通过的 (DVL) 或G蛋白发出信号. 我们的研究表明,FZD5中的保留残留物对于选择信号通路至关重要,这表明形状变化决定了传感器的选择.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 结构生物学 结构生物学
背景情况:
- 色受体 (FZD) 是一种G蛋白结合受体 (GPCRs) 的类型,对于各种生物过程至关重要.
- FZD受体通过分离 (DVL) 或异构三基G蛋白发出信号,但通路选择的机制尚不清楚.
研究的目的:
- 研究FZD5中保存残留物在指定的信号通路中的作用.
- 了解FZD受体结构如何影响信号传导结果.
主要方法:
- 在FZD5.5的结构驱动性突变发生.
- 广泛的功能信号测试.
- 对FZD5变体进行比较的分子动力学模拟.
主要成果:
- 在FZD5中保存的残留物对于信号路径选择至关重要.
- FZD5和相关的FZD受体优先与DVL相结合,而不是G蛋白.
- 在FZD受体中明显的活性状态构造变化决定了转换器的选择性.
结论:
- 的受体利用特定的微开关来选择信号通路.
- FZD受体的形态动态对于定义它们与下游信号合作伙伴的相互作用至关重要.
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