Molecular Mechanism of Ligand Recognition and Activation of Lysophosphatidic Acid Receptor LPAR6

January 2025 in “ Proceedings of the National Academy of Sciences ”

Yaning Duan, Zhenmei Xu, Boyu Hao, Anqi Zhang, Changyou Guo, Yuanzheng He

lysophosphatidic acid LPAR6 G-protein coupling transmembrane helix extracellular loop EDG family non-EDG family

TLDR LPAR6 has a unique way of binding and activating, which helps in designing treatments for hair loss and cancer.

This study explores the molecular mechanisms of ligand recognition and activation of the lysophosphatidic acid receptor LPAR6, which is relevant for hair loss and cancer treatment. Using cryoelectron microscopy, researchers identified a unique ligand binding mode in LPAR6, distinct from LPAR1, highlighting structural differences in the ligand-binding pocket and phosphate head group engagement. The study also examines the receptor's activation process and G-protein coupling, showing a strong association with G13 and primarily hydrophobic engagement with Gq. These findings provide a framework for drug design targeting LPAR6, with potential applications in treating hair loss and cancer.

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research Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, P2Y5/LPA6

253 citations , April 2009 in “Journal of Biological Chemistry”

p2y5, now called LPA6, is a receptor important for human hair growth.

research Disruption of P2RY5, an Orphan G Protein–Coupled Receptor, Underlies Autosomal Recessive Woolly Hair

210 citations , February 2008 in “Nature genetics”

Mutations in the P2RY5 gene cause autosomal recessive woolly hair.