title: Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli.
abstract: Animals utilize hundreds of distinct G protein-coupled receptor (GPCR)-type chemosensory receptors to detect a diverse array of chemical signals in their environment, including odors, pheromones, and tastants. However, the molecular mechanisms by which these receptors selectively interact with their cognate ligands remain poorly understood. There is growing evidence that many chemosensory receptors exist in multimeric complexes, though little is known about the relative contributions of individual subunits to receptor functions. Here, we report that each of the two subunits in the heteromeric T1R2:T1R3 sweet taste receptor binds sweet stimuli though with distinct affinities and conformational changes. Furthermore, ligand affinities for T1R3 are drastically reduced by the introduction of a single amino acid change associated with decreased sweet taste sensitivity in behaving mice. Thus, individual T1R subunits increase the receptive range of the sweet taste receptor, offering a functional mechanism for phenotypic variations in sweet taste.
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Nie
authors.forename: Stephan
authors.initials: S
authors.lastname: Vigues
authors.forename: Jeanette R
authors.initials: JR
authors.lastname: Hobbs
authors.forename: Graeme L
authors.initials: GL
authors.lastname: Conn
authors.forename: Steven D
authors.initials: SD
authors.lastname: Munger
mesh_terms: D000818:Animals; D002846:Chromatography, Affinity; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors / Q000235:genetics; D008024:Ligands; D051379:Mice; D016297:Mutagenesis, Site-Directed; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D013050:Spectrometry, Fluorescence; D013057:Spectrum Analysis; D013549:Sweetening Agents / Q000378:metabolism*; D013649:Taste / Q000502:physiology*
chemical_list: D017931:DNA Primers; D008024:Ligands; D021122:Protein Subunits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; C431926:taste receptors, type 1