Figure 2.

Energy relationships among the conformational states. (A) Intrinsic equilibrium among the conformations of the GPCR molecules in the absence of agonists, antagonists, transfer proteins, or allosteric modulators. Under these conditions the B state is more stable than the A states (shown here with equal stabilities). (B) The redistribution of A_blue and A_red states in the presence of a biased agonist (in this case favoring the A_red state). Both states are stabilized, but A_red is moreso than A_blue. The B state is not shown. (C) Molecules are shown as in (B), with the addition of transfer proteins, G-protein and β-arrestin. Each transfer protein can bind to both the A_blue and A_red states, but only the preferential binding partners are presented here. An additional stabilization of the A_red state arises from the binding energy provided by β-arrestin. (D) The case of an unbiased agonist (gray diamond) bound in the presence of a biased positive allosteric modulator that favors the A_blue state. To see this figure in color, go online.