Fig. 8: Changes in CaSR dynamics by mutation predict calcium sensitivity.

a Surface representation of CaSR (PDB 5K5T) with known sensitizing (green) and desensitizing (red) mutations mapped to the structure. b Barbell plot showing the center of the FRET distribution in the inactive condition (10 mM EDTA, gray) and active condition (10 mM Ca²⁺ + 5 mM l-Trp, purple) for CaSR mutants. Mutants that desensitize (red) or sensitize the receptor (green) are grouped together. The amplitude of the FRET shift is shown on the right. c Amplitude of receptor cross correlation of wild-type (gray), sensitizing (green) mutations, and desensitizing (red) mutations in the presence of 10 mM EDTA or 10 mM Ca²⁺. Data represent mean ± s.e.m. of n = 3 independent biological replicates. d schematic conformational energy landscape of CaSR in the absence of ligand (black) and in the presence of Ca²⁺ (red). e Model of CaSR illustrating how the LB2 surface charge modulates sensitivity. As the LB2 becomes more positive, the stability of the active interface increases resulting in increased receptor sensitivity.