a, Overall structure of the symmetric CaSR–NAM–Ca2+–Trp 7TMs. b, Comparison of the symmetric CaSR–NAM–Ca2+–Trp 7TMs (grey) and the asymmetric PAM-bound 7TMs (7TMA (green) and 7TMB (blue)) based on 7TMB alignment. c, Conformational changes in CaSR TM6. d, Conformational changes in the 5HT2A serotonin receptor (Protein Data Bank (PDB): 6A94 and 6WHA), a family A GPCR that couples to Gq in a similar way to CaSR. e, Sequence logo analysis of family C and family A TM6 regions highlighting the conservation of toggle switch motif residues.