Molecular Mechanism for the Umami Taste Synergism

• Published in: Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (52), p.20930-20934
• Main Authors: Zhang, Feng, Klebansky, Boris, Fine, Richard M., Xu, Hong, Pronin, Alexey, Liu, Haitian, Tachdjian, Catherine, Li, Xiaodong
• Format: Article
• Language: English
• Subjects: Binding sites; Binding Sites - physiology; Biological Sciences; Cell Line; Cell lines; Dose response relationship; Glutamic Acid - chemistry; Glutamic Acid - genetics; Glutamic Acid - metabolism; HEK293 cells; Humans; Ligands; Metabotropic glutamate receptors; Models, Molecular; Molecular biology; Multiprotein Complexes - chemistry; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Mutagenesis; Mutagenesis, Site-Directed; Protein Binding - physiology; Protein Structure, Quaternary - physiology; Receptors; Receptors, G-Protein-Coupled - chemistry; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Ribonucleotides - chemistry; Ribonucleotides - genetics; Ribonucleotides - metabolism; Sweeteners; Taste; Taste - physiology; Umami
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0810174106

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.