TM dimer interface of the active CaS receptor. (A and B) TM dimer interface formed by TM6 of both subunits in the PAM-bound (A) and PAM-free (B) states. Magnified panels depict direct contacting residues viewed from the extracellular end or the side. (C) Functional analysis of the TM dimer interface. Dose-dependent Ca2+-stimulated IP1 accumulation was measured in cells transiently expressing either WT or mutant CaS receptor bearing one of the selected substitutions at the core TM interface. Cell-surface expression levels of the I816A, S820A, S820F, P823A, A824V, and T828N mutants were 78, 71, 91, 100, 69, and 93% of WT level, respectively. Data points represent the average ± SEM of multiple experiments (n), each with triplicate measurements.