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.