G protein-coupled receptors (GPCRs) represent one of the largest and most therapeutically important families of membrane proteins, regulating diverse physiological processes and serving as major targets for drug discovery. Recent advances in structural biology, including cryo-electron microscopy (cryo-EM), have transformed our understanding of GPCR activation mechanisms and ligand recognition. However, obtaining high-quality, stable GPCR samples suitable for biochemical and structural studies remains technically challenging due to difficulties associated with membrane protein expression, purification, stabilization, and functional validation.

This Topical Collection will highlight current and emerging methodologies for the production and characterization of GPCRs and GPCR signaling complexes. The collection will provide practical protocols covering heterologous expression systems, including mammalian and insect platforms, optimization of receptor expression, membrane preparation, detergent and lipid selection, affinity purification strategies, and size exclusion chromatography approaches for obtaining homogeneous protein complexes. Additionally, methods for receptor stabilization using G protein, mini-G protein, nanobodies, and engineered binding partners will be explored.