Stabilising biased allosteric G protein-coupled receptor conformations

The current proposal seeks to develop and identify novel molecules that can stabilise distinct calcium sensing receptor (CaSR) conformations. The CaSR is a G protein-coupled receptor (GPCR) essential for the life of vertebrates. GPCRs are responsible for virtually all (patho)physiological processes. They are structurally very flexible, which underlies their activity, but this has also hindered their structural determination. Development and validation of the proposed molecules will aid future structural studies of an important GPCR. Thus, the proposed research will enhance our fundamental understanding of the structure and function of the CaSR, and ultimately of the vital GPCR superfamily.