Functional characterization of the ligand binding domain of the cat T1R1 taste receptor

The umami taste receptor is a heterodimeric G-protein coupled receptor (GPCR), composed of two subunits called T1R1 and T1R3. Both subunits are class C GPCRs whose members share a common architecture composed of a large N-terminal domain (NTD) connected to a heptahelical transmembrane domain by a short cysteine-rich domain. Cellular assays combined with molecular docking and site-directed mutagenesis studies have revealed that the NTD of the T1R1 subunit contains the primary binding site for umami stimuli, such as L-glutamate (L-Glu) for humans. Inosine-5’-monophosphate (IMP) binds close to the opening of the NTD, responsible for the characteristic umami synergy between L-Glu and IMP. Funct…