Fig. 5.

Location of mutations in the hGnRHR. Helices are shown by cartoons colored blue (inactive conformation) and yellow (active conformation). Substituted residues are shown by sticks, highlighted by dots, and colored purple (inactive conformation) and orange (active conformation). A, Positions of residues mutated in this work (E⁹⁰K, F²⁷²Q, K, C²⁷⁹A, S, Y²⁸⁴F, and ΔK¹⁹¹) in inactive and active conformations of hGnRHR. Side chains of substituted residues (E⁹⁰, F²⁷², C²⁷⁹, and Y²⁸⁴) are shown by balls colored purple (for the inactive state) and orange (for the active state). K¹⁹¹ from the EL2 and proximal N¹⁸ from the N terminus are shown by sticks colored blue. B, Suggested changes in the ligand binding pocket on receptor activation. Positions of mutated residues (C²⁷⁹ and Y²⁸⁴) in the binding pocket of active (yellow) and inactive (blue) receptor conformations. Helix shift and rotamer change of Y²⁸⁴ and C²⁷⁹ during the receptor activation bring Y²⁸⁴ to the nonpolar lipid environment and C²⁷⁹ to the polar environment of the ligand binding pocket. Note the contraction of the ligand binding pocket in the active state caused by the inward movement of TM5, TM3, and TM7. C–J, Interactions between substituted residues in position 272 from the moving TM6 and adjacent residues from TM3, TM5, and TM7 in the model of the inactive and activated hGnRHR. Environment of F²⁷² of hGnRHR (C and G) and its substitutions, F²⁷²L (D and H), F²⁷²Q (E and I), and F²⁷²K (F and J), in inactive (C–F, blue) or active (G–J, yellow) receptor states.