Refining G protein-coupled receptor biochemistry to obtain challenging cryogenic electron microscopy structures

G protein-coupled receptors (GPCRs) are proteins that are involved in most aspects of human health. GPCRs transmit signals from the outside of the cell to the inside. In order to accomplish this, they must be activated (by hormones or drugs) and undergo a complicated change in shape. Cryogenic electron microscopy (cryo-EM) has given us unprecedented insight into the ‘what’ and ‘how’ of these shape changes. However, we still don’t know ‘why’ some drugs only partially activate GPCRs. We also don’t know how rare mutations of GPCRs change their function. My project extended cryo-EM techniques to uncover some of these details.