Fig. 7: Schematic illustration of signaling interactions of the CeLGR and hTSHR receptors. (Upper panels) Views along the receptor dimer axis from outside the cellular membrane, showing only ECDs of receptor. (Lower panels) Views from within the membrane after 90° rotations as indicated by the arrows of rotation.
From: Structure of an LGR dimer, an evolutionary predecessor of glycoprotein hormone receptors
The receptor ECD and TMD domains are depicted as yellow rectangles; the heterodimeric hormones are depicted as red rectangles; and the heterotrimeric G proteins are depicted respectively as green and blue rectangles for Gs and Gq, but not to scale. (Left pair) An asymmetric receptor dimer (142° rotation; 4 Å translation) in the apo state (0H:2 R) is shown oriented as for CeLGR in Fig. 1a (lower) and 1c (upper). (Center pair) An asymmetric dimer having one hormone bound (1H:2R) is shown as for the Aup/Bdown model in Supplementary Fig. 12, which has protomer A in its upright pose as for the TSH:TSHR complexes but with Ceα2β5 replacing TSH. The hormone bound to protomer A blocks the binding site on protomer B; thus, only one hormone can bind. (Right pair) The receptor model accommodates two hormone molecules equivalently after symmetrization to a simple 180° rotation. The equilibria defined by KEq1 and KEq2 refer to intrinsic conformational transitions of the receptor. The hormone binding equilibria, defined by Kd1 for the first hormone binding event and by Kd2 for the second, incorporate penalties that must be met in surmounting energetic barriers for achieving the respective hormone-receptive conformations.
