Taking advantage of constitutive activity for structural determination of ligand free GPCRs

Receptors within our bodies are typically activated by a stimulus, however, in some conditions, receptors are able to be activated without any external activator, which is called constitutive activity. This can be achieved by changes to the receptors that make it easier for the receptor to form its active conformation and signal. Two such receptors are the parathyroid hormone receptor 1 (PTH1R), where constitutively active mutations are linked to Jansen’s metaphyseal chondrodysplasia; and GPR3, a receptor who's native agonist remains unknown. In this thesis, I will use cryogenic electron microscopy to study constitutive activity at both receptors. By doing so, we will gain a deeper understanding to their roles in health and also disease.