Calcium Sensing Via The Calcium-Sensing Receptor and Designed Calcium Sensors

Calcium functions as a universal messenger, regulating numerous biological and pathological processes of organisms and cells. The calcium-sensing receptor is a major protein that responds to extracellular calcium concentration and metabolites to trigger calcium changes inside cells and regulates multiple signaling pathways and diseases. The research presented in this thesis was designed to interpret the presumed role of CaSR in regulating calcium homeostasis and to understand the binding and functional cooperativity of CaSR that contains Ca2+-binding sites within the CaSR-ECD. The second part of this thesis illustrates optimizing functional assays to identify CaSR therapeutics based on a novel allosteric modulator, TNCA. Third, novel calcium sensors such as R-CatchER and G-CatchER+, designed in the Yang lab with unique capabilities to measure rapid calcium responses at the ER, were expressed/purified for biophysical characterization. These studies provide insights into the molecular basis for CaSR-related diseases to facilitate the discovery of new therapeutics