This inaugural lecture will be given by Professor Mark Wheatley of the School of Biosciences, College of Life and Environmental Sciences.
G-protein-coupled receptors (GPCRs) form a large superfamily of structurally-related proteins that mediate their effects by coupling to G-proteins. They are one of the largest families in the human genome, are fundamentally important for cell signalling and are a major target for drug discovery. Indeed, 40-50 % of clinically-marketed drugs are active at this receptor family. A fundamental issue in molecular pharmacology today is defining, at the molecular level, how GPCRs are activated. Despite being activated by a wide variety of stimuli from photons to large glycoproteins, these receptors exhibit a conserved protein architecture comprising a bundle of seven transmembrane helices linked by extracellular and intracellular loops. The complementary approaches of specific mutagenesis, chimeric constructs, molecular modelling and peptide chemistry have been employed to identify important residues and domains required for activation of GPCRs by hormones and to provide insight into how this can be selectively blocked by specific compounds. This research will increase our understanding of cell-cell communication and will aid rational drug design in the future.