Extended Data Fig. 6: Molecular dynamics simulations showing hormone-induced receptor activation.

a, Representative snapshots from the CG-bound receptor simulation and inactive receptor simulation, respectively. The receptor is shown as cartoon, the CG is shown as surface, the phosphate groups of the lipid membrane are shown as spheres, three ECD residues N107, D157 and E206 are shown as sticks. b, Changes of ECD orientations observed in the different simulations as a function of time. Tilting angle of the ECD with respect to the z-axis (membrane normal) and the minimal distance from an ECD residue (D157, N107, or E206) to the membrane. c, Structural alignment of the CG–LHCGR complex onto the FSH–FSHR-ECD dimer (PDB code: 1WXD, left panel) shows that the two TMD from each complex is pointed in the opposite direction and cannot be on the same membrane layer. d, Structural alignment of the CG–LHCGR complex onto the FSH–FSHR-ECD trimer (PDB code: 4AY9, right panel) shows that the TMD from the CG–LHCGR complex will clash with the neighbouring ECD in the trimeric arrangement. The trimeric FSH–FSHR ECD was shown in surface presentation, with each monomeric complex in a single colour (red, yellow, green). The CG–LHCGR is shown as a ribbon and is aligned onto the yellow ECD complex but is clashed with the red ECD complex.