Fig. 5

Pi-binding sites in the CaSR extracellular domain. Pi-binding sites in the CaSR’s active and inactive conformations. In the active conformation (left), R62 and R66 interact respectively with E277 (creating a salt bridge) and S302 (hydrogen bond) to keep the upper and lower domain closely associated ensuring a closed/active conformation. In the inactive conformation (right), both interactions are broken and Pi ions stabilize the positive charges of R62 and R66. Also, Pi ions displace a lower domain eliciting an open/inactive conformation, by reducing equilibrium free energy. Note that Pi-binding site 1 is only occupied in the inactive state, whereas Pi-binding site 2 is occupied in both inactive and active conformations integrated within the receptor’s structure. Pink sticks show the R62–E277 salt bridge interaction and green sticks show the R66–S301 hydrogen bond. PDB accession numbers 5k5s and 5k5t²⁷. BS binding site