Extended Data Fig. 6: Asymmetric dimer interface of CaSR in the active state and in G-protein-coupled states.
From: Allosteric modulation and G-protein selectivity of the Ca2+-sensing receptor
a, Structural comparison between active-state CaSR in detergent (PDB ID: 7M3F) and lipid nanodiscs. The ECDs in the two structures show different tilting angles relative to the 7TMs. b, Structural comparison between the CINA-bound CaSR–Gi and CaSR–Gq complexes in nanodiscs. The 7TMs (except the cytoplasmic regions) and the bound ligands are well aligned. c, The VFT of the NGC protomer of the CINA-bound CaSR–Gi or CaSR–Gq complex is aligned to the VFT of the GC protomer. d, The asymmetric TM6–TM6 interface in the structure of CINA-bound active-state CaSR in nanodiscs. e,f, The asymmetric 7TM interface in the structure of the CINA-bound CaSR–Gi in nanodiscs shown in two views, highlighting the interface between TM6 of 7TMNGC and TM6 of 7TMGC (e), and the interface between TM5 and TM6 of 7TMGC and TM7 of 7TMNGC (f). The residues that are involved in dimer interactions, and the models of phospholipids (DOPC) and cholesterol are shown. g, Functional responses of CaSR WT and mutants to Ca2+, for Gi3 and Gq activation, categorized based on interactions with the lower (F776A, K805A, F806A and F809A) and upper (I822A, Y825A, Y829A and V833A) phospholipids.
