a, size-exclusion chromatography profile of purified CaSR. b, BRET-based assay40 monitoring Gq activation by CaSR upon Ca2+ addition. n = 3 independent experiments, data represent mean ± s.e.m. c–f, Functional responses of CaSR to Ca2+ alone or in combination with PAMs or NAM measured by IP1 accumulation assays. n = 3 independent experiments, data represent mean ± s.e.m. g, Cryo-EM map and model of inactive state CaSR complexed with NAM. h, Cryo-EM map and model of the CaSR-NAM-Ca2+-Trp complex. i, Structure of the inactive-state CaSR ECD region showing an open-closed inactive VFT configuration.