The goal of this application is to understand how amino acid taste stimuli specifically interact with T1R taste receptors. T1R1 and T1R3 function as a heteromeric receptor to detect umami stimuli such as L-amino acids. Both subunits belong to the Class C GPCR family, whose members exhibit a long N-terminal domain (NTD) that is the likely site of ligand interaction. For the T1R1 :T1 R3 umami receptor, the interaction of ligand and receptor is so selective that it can discriminate between two enantiomers of the same amino acid. The stereospecificity for L-amino acids is dependent on T1R1, as T1R3 is also a component of the receptor for sweet stimuli, including some D-amino acids. This study has two main components. First, I will test whether L-amino acids and other umami stimuli interact with the NTD of T1R1 by using Synchroton Radiation Circular Dichroism (SRCD) spectroscopy and spectrofluorescence. Second, I will determine whether polymorphisms in the T1R1 NTD that correlate with L-glutamate taste sensitivity between mouse strains, affect the ability of T1R to bind amino acid ligands. Using highly innovative approaches, these studies will not only illuminate the contribution of receptor structure to ligand selectivity in gustation but will also provide important insights into the structural basis of ligand-receptor interactions in many amino acid receptor systems. The processed food available in our society is commonly flavor enhanced to be more attractive to consumers. While more sugar or monosodium glutamate (MSG) can enhance the palatability of food, their excessive ingestion can lead to obesity or hormonal deregulation. Understanding the way ligands interact with taste receptors could lead to the discovery of new food additives with no or fewer side effects. ? ? ?
| Dotson, Cedrick D; Vigues, Stephan; Steinle, Nanette I et al. (2010) T1R and T2R receptors: the modulation of incretin hormones and potential targets for the treatment of type 2 diabetes mellitus. Curr Opin Investig Drugs 11:447-54 |
| Vigues, S; Dotson, C D; Munger, S D (2009) The receptor basis of sweet taste in mammals. Results Probl Cell Differ 47:187-202 |
| Dotson, Cedrick D; Zhang, Lan; Xu, Hong et al. (2008) Bitter taste receptors influence glucose homeostasis. PLoS One 3:e3974 |
