Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin with the T1R2‐T1R3 receptor

Sweet tasting proteins interact with the same receptor that binds small molecular weight sweeteners, the T1R2-T1R3 G-protein coupled receptor, but the key groups on the protein surface responsible for the biological activity have not yet been identified. I propose that sweet proteins, contrary to small ligands, do not bind to the 'glutamate-like' pocket but stabilize the free form II of the T1R2-T1R3 receptor by attachment to a secondary binding site. Docking of brazzein, monellin and thaumatin with a model of the T1R2-T1R3 sweet taste receptor shows that the most likely complexes can indeed stabilize the active form of the receptor.