Elucidation of GPCR-G protein selectivity by cryo-electron microscopy

Two-thirds of our hormones and one-third of drugs act by modulating receptors that activate cellular signal proteins called G proteins. It is a mystery how only four families of G proteins can mediate the diverse physiological and pharmaceutical responses of hundred as many receptors. Clues are emerging from 3D molecular structures of receptor-G protein complexes, but these are way too few. This project will fund the latest state-of-the-art equipment to prepare such receptor-G protein complexes for cryogenic electron microscopy, which is a new method that has revolutionised our ability to obtain challenging protein structures. This will lead to a better understanding of human signalling and uncover molecular mechanisms to steer the cellular signalling to design safer and more potent