 The receptor theory states that the effect of a ligand depends on its concentration, but the response to pheromones in yeast is not affected by changes in their abundance. This robustness is attributed to the fact that the fraction of occupied receptors is measured rather than the total number of receptors. The model suggests that this fractional occupancy is determined by the physical interaction between the inhibitor of G-protein signaling, SST2, and the receptor. Replacing the endogenous RGS protein, SST2, with a mutant version that cannot interact with the receptor abolishes the robustness. Furthermore, forcing the interaction between the mutated RGS protein and the receptor restores the robustness. These findings suggest that the receptor pathway measures the fraction of bound ligands and uses this information to determine the strength of the signal. This article was authored by Ellen Bush, Gustavo Varsen, Andreas Konstantina, and others.