Molecular mechanism for the umami taste synergism

TLDR

Umami, one of the five basic taste qualities, is mediated by the heteromeric T1R1/T1R3 receptor complex and is markedly enhanced by 5′‑ribonucleotides binding to L‑glutamate, a hallmark synergy of this taste. The study aims to elucidate the molecular mechanism of umami synergy using chimeric T1R receptors, site‑directed mutagenesis, and molecular modeling. The authors propose a cooperative ligand‑binding model in which L‑glutamate binds near the hinge of T1R1’s Venus flytrap domain while 5′‑ribonucleotides bind adjacent to the opening, stabilizing the closed conformation. The proposed mechanism may extend to other class C G‑protein‑coupled receptors.

Abstract

Umami is one of the 5 basic taste qualities. The umami taste of L-glutamate can be drastically enhanced by 5' ribonucleotides and the synergy is a hallmark of this taste quality. The umami taste receptor is a heteromeric complex of 2 class C G-protein-coupled receptors, T1R1 and T1R3. Here we elucidate the molecular mechanism of the synergy using chimeric T1R receptors, site-directed mutagenesis, and molecular modeling. We propose a cooperative ligand-binding model involving the Venus flytrap domain of T1R1, where 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 unique mechanism may apply to other class C G-protein-coupled receptors.