National Natural Science Foundation of China (NSFC)
32171201
China
Citation
Journal: Nat Commun / Year: 2025 Title: Structural basis of human VANGL-PRICKLE interaction. Authors: Yanyi Song / Shuyi Jian / Junlin Teng / Pengli Zheng / Zhe Zhang / Abstract: Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric ...Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric distribution of two core protein complexes on opposite sides of the cell membrane. The Van Gogh-like (VANGL)-PRICKLE (PK) pair is one of these two key regulators; however, their structural information and detailed functions have been unclear. Here, we present five cryo-electron microscopy structures of human VANGL1, VANGL2, and their complexes with PK1 at resolutions of 2.2-3.0 Å. Through biochemical and cell imaging experiments, we decipher the molecular details of the VANGL-PK interaction. Furthermore, we reveal that PK1 can target VANGL-containing intracellular vesicles to the peripheral cell membrane. These findings provide a solid foundation to understand the explicit interaction between VANGL and PK while opening new avenues for subsequent studies of the PCP pathway.
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