Post by Basic & Clinical Pharmacology & Toxicology

⭐ July Editor's Pick How do chemoattractants activate their receptors to guide immune cell trafficking? A new study by Yang and colleagues provides compelling evidence that GPR25 is a bona fide receptor for CXCL17 and proposes a novel two-step mechanism of activation. Using mutagenesis and molecular modelling, the authors show that the N-terminus of GPR25 first tethers and orients CXCL17, while the C-terminus of CXCL17 subsequently activates the receptor through an intrahelical binding pocket. The study also identifies W95, R178 and R264 as residues essential for signalling and suggests that CXCL17 may function through a distinct activation paradigm rather than as a classical chemokine. 🎯 Why this matters Understanding how chemoattractants activate their receptors is fundamental to immune cell trafficking. By elucidating the CXCL17–GPR25 signalling axis, this study advances our understanding of GPCR activation mechanisms and may open new avenues for research into immune regulation and inflammatory diseases. 🔬 This paper is selected as July Editor's Pick because it adds an important piece to our understanding of GPCR activation mechanisms and immune cell trafficking. By combining structural modelling with functional validation, the study provides valuable mechanistic insight while highlighting the biological relevance of the CXCL17–GPR25 signalling axis. Congratulations to Wuqing Yang, Sean P. Giblin and James Pease at Imperial College London! Read the paper here: https://lnkd.in/eTacgEQM #chemokine #GPCR #GPR25 #modelling