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使用BRET生物传感器进行全类范围的Frizzled-Dishevelled交互分析,揭示了受体对应物之间的功能差异

Lukas Grätz¹, Jan H Voss¹, Gunnar Schulte¹

¹Department of Physiology & Pharmacology, Section of Receptor Biology & Signaling, Biomedicum, Karolinska Institutet, S-17165 Stockholm, Sweden.

|August 30, 2024

概括

无翼/Int-1 (WNT) 信号传输涉及Frizzleds (FZD) 与Dishevelled (DVL) 进行交互. 这项研究揭示了动态的FZD/DVL相互作用和配体选择性,为针对FZD的药物发现提供了新的见解.

科学领域:

细胞信号传递途径细胞信号传递途径
分子和结构生物学分子和结构生物学.

背景情况:

无翼/Int-1 (WNT) 信号传递对细胞过程至关重要,由Frizzled (FZD) 受体结合WNT连接体进行介导.
FZDs和信号传感器Dishevelled (DVL) 之间的相互作用是关键的,但FZD选择性和paralog特定差异仍然不清楚.

研究的目的:

为了研究全类的FZD/DVL相互作用动态和配体选择性.
开发新型生物传感器,用于对FZD向治疗的高通量查.

主要方法:

使用生物发光共振能量转移 (BRET) 技术,使用单分子FZD/DVL DEP域传感器.
分析了不同FZD类型的构成性和体刺激的FZD/DEP相互作用.

主要成果:

大多数Frizzleds表现出与DVL DEP域的构成性高亲和互动.
连接体刺激揭示了动态的FZD/DEP接口,在连接体选择性和信号动力学中具有明显的相对对应特异性.
开发的单分子传感器适用于高通量选.

结论:

阐明了FZD和DVL之间全沟通的机制差异.
新型受体专注生物传感器促进了针对FZD的药物发现和开发.

关键词:

乱的,没有整齐的.毛的毛的在GPCR中,GPCR是指GPCR.在WNT中使用WNT.生物发光共振传输能量转移.F 类F 类F 类转换器转换器转换器

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