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Structure-function relationships of GALR2 signalling


G protein coupled receptors (GPCRs) are transmembrane proteins with essential roles in physiology and disease. They enable cells to respond to stimuli by ligands, such as peptides, neurotransmitters, lipids, hormones, carbohydrates, glycoproteins, ions, photons and odorants, and are the targets of many drugs used in the clinic. The signalling pathways and protein structures associated with selected GPCRs have been explored in depth. However, pathways associated with peptide stimulated GPCRs, such as the galanin receptor 2 (GALR2), remain poorly understood despite their important physiological roles. GALR2 is involved in a range of processes including nociception, memory, intestinal secretion and contractility and deficiencies in the galanin-GALR2 axis are linked to pathologies such as cancer and multiple sclerosis. This proposal aims to deliver fundamental new information on the molecular pharmacology and structure of GALR2, which can in the future be used to develop approaches for its pharmacological modulation. In addition, this project will strengthen an existing UK-Brazil collaboration and consolidate GPCR structure elucidation by cryo-EM in Brazil. (AU)

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