Molecular mechanism for the umami taste synergism.
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.
Zhang
Feng
F
Senomyx, Incorporated, 4767 Nexus Centre Drive, San Diego, CA 92121, USA.
Klebansky
Boris
B
Fine
Richard M
RM
Xu
Hong
H
Pronin
Alexey
A
Liu
Haitian
H
Tachdjian
Catherine
C
Li
Xiaodong
X
D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D018698:Glutamic Acid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding / Q000502:physiology; D020836:Protein Structure, Quaternary / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013649:Taste / Q000502:physiology*
D046912:Multiprotein Complexes; D043562:Receptors, G-Protein-Coupled; D012265:Ribonucleotides; C431926:taste receptors, type 1; D018698:Glutamic Acid