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A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways

Cell Discov .. 2024-01; 
Zhibin Zhang , Xi Lin , Ling Wei , Yiran Wu , Lu Xu , Lijie Wu , Xiaohu Wei , Suwen Zhao, Xiangjia Zhu , Fei Xu
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Codon Optimization The codon-optimized nucleotide sequence of human Frizzled-1 (FZD1; Uniprot ID: Q9UP38), Frizzled-3 (FZD3; Uniprot ID: Q9NPG1) and Frizzled-6 (FZD6;Uniprot ID: O60353) were synthesized by GenScript. Get A Quote

摘要

The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested... More

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