T1R receptors mediate mammalian sweet and umami taste

The T1R family of taste receptors mediates 2 taste qualities: T1R2/T1R3 for sweet taste and T1R1/T1R3 for umami taste. Functional expression in heterologous system and gene knockout studies has shown their functions as taste receptors. Structure-function relation studies on T1R2/T1R3 showed multiple ligand binding sites on both subunits. The umami taste of l-glutamate can be drastically enhanced by 5' ribonucleotides, and the synergy is a hallmark of this taste quality. On the basis of chimeric T1R receptors, site-directed mutagenesis, and molecular modeling data, we recently proposed a cooperative ligand binding model that involved the Venus flytrap domain of T1R1 in which l-glutamate binds close to the hinge region and 5' ribonucleotides bind to an adjacent site close to the opening of the flytrap to further stabilize the closed conformation. This novel mechanism may apply to other class C, G protein-coupled receptors.