JAPANESE TOP Message from the Director Information Faculty list Research Projects International Conference Entrance Exam Visitors Publication Job Vacancy International Partnerships Links Access HANDBOOK FOR INTERNATIONAL RESEARCHERS Map of Inuyama
BONOBO Chimpanzee "Ai" Crania photos Itani Jun'ichiro archives Guidelines for Care and Use of Nonhuman Primates(pdf) Study material catalogue/database Guideline for field research of non-human primates Primate Genome DB

Primate Research Institute, Kyoto University
Inuyama, Aichi 484-8506, JAPAN
TEL. +81-568-63-0567
(Administrative Office)
FAX. +81-568-63-0085

Copyright (c)
Primate Research Institute,
Kyoto University All rights reserved.



Two Distinct Determinants of Ligand Specificity in T1R1/T1R3 (the Umami Taste Receptor)

Yasuka Toda, Tomoya Nakagita, Takashi Hayakawa, Shinji Okada, Masataka Narukawa, Hiroo Imai, Yoshiro Ishimaru, and Takumi Misaka

Umami taste perception in mammals is mediated by a heteromeric complex of two G-protein-coupled receptors, T1R1 and T1R3. T1R1/T1R3 exhibits species-dependent differences in ligand specificity; human T1R1/T1R3 specifically responds to L-Glu, whereas mouse T1R1/T1R3 responds more strongly to other L-amino acids than to L-Glu. The mechanism underlying this species difference remains unknown. In this study we analyzed chimeric human-mouse receptors and point mutants of T1R1/T1R3 and identified 12 key residues that modulate amino acid recognition in the human- and mouse-type responses in the extracellular Venus flytrap domain of T1R1. Molecular modeling revealed that the residues critical for human-type acidic amino acid recognition were located at the orthosteric ligand binding site. In contrast, all of the key residues for the mouse-type broad response were located at regions outside of both the orthosteric ligand binding site and the allosteric binding site for inosine-5-monophosphate (IMP), a known natural umami taste enhancer. Site-directed mutagenesis demonstrated that the newly identified key residues for the mouse-type responses modulated receptor activity in a manner distinct from that of the allosteric modulation via IMP. Analyses of multiple point mutants suggested that the combination of two distinct determinants, amino acid selectivity at the orthosteric site and receptor activity modulation at the non-orthosteric sites, may mediate the ligand specificity of T1R1/T1R3. This hypothesis was supported by the results of studies using nonhuman primate T1R1 receptors. A complex molecular mechanism involving changes in the properties of both the orthosteric and non-orthosteric sites of T1R1 underlies the determination of ligand specificity in mammalian T1R1/T1R3.

The Journal of Biological Chemistry Vol. 288, No. 52, pp. 36863–36877, 2013



Copyright(C) 2012 PRI (). All rights reserved.