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Published on: December 26, 2011
Structural and Druggability Landscape of Frizzled G Protein-Coupled Receptors
Xianjun Zhang1, Shaowei Dong1, Fei Xu2
1iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
Class Frizzled G protein-coupled receptors (GPCRs), which includes the Smoothened receptor (SMO) and 10 Frizzled receptors (FZDs), are responsible for mediating fundamental signaling in embryonic development and tissue homeostasis. Dysregulation of these receptors can lead to cancer. Structural understanding of these molecules has provided insight to their function and signaling, and guided drug discovery. To date, the structures of the multi- and individual domains of SMO, 14 FZD extracellular domains, and the transmembrane domain (TMD) of FZD4, have been reported. Here, we review all reported frizzled family structures and diverse signalosome models, with an emphasis on the different ligand binding sites and lipid binding grooves, aiming to uncover the druggability landscape of the frizzled GPCR family.
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