The Frizzled family of transmembrane receptors (FZD) belongs to the class F of G protein-coupled receptors (GPCRs). FZDs bind to and are activated by Wingless/Int1 (WNT) proteins. The WNT/FZD signaling system regulates crucial aspects of developmental biology and stem-cell regulation. Dysregulation of WNT/FZD communication can lead to developmental defects and diseases such as cancer and fibrosis. Recent insight into the activation mechanisms of FZDs has underlined that protein dynamics and conserved microswitches are essential for FZD-mediated information flow and build the basis for targeting these receptors pharmacologically. In this review, we summarize recent advances in our understanding of FZD activation, and how novel concepts merge and collide with existing dogmas in the field.

中文翻译：

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卷曲作为动态药理实体

Frizzled 跨膜受体家族 (FZD) 属于 G 蛋白偶联受体 (GPCR) 的 F 类。 FZD 与 Wingless/Int1 (WNT) 蛋白结合并被其激活。 WNT/FZD 信号系统调节发育生物学和干细胞调节的关键方面。 WNT/FZD 通讯失调可导致发育缺陷和疾病，例如癌症和纤维化。最近对 FZD 激活机制的深入了解强调，蛋白质动力学和保守的微开关对于 FZD 介导的信息流至关重要，并为药理学上靶向这些受体奠定了基础。在这篇综述中，我们总结了对 FZD 激活的理解的最新进展，以及新颖的概念如何与该领域现有的教条融合和碰撞。