The structural basis of L-amino acid taste

描述（由申请人提供）：本申请的目的是了解氨基酸味觉刺激物如何与T1 R味觉受体特异性相互作用。T1 R1和T1 R3作为异聚体受体发挥功能，以检测鲜味刺激物，如L-氨基酸。这两个亚基都属于C类GPCR家族，其成员表现出长的N-末端结构域（NTD），这是配体相互作用的可能位点。对于T1 R1：T1 R3鲜味受体，配体和受体的相互作用是如此选择性，以至于它可以区分相同氨基酸的两种对映体。L-氨基酸的立体特异性取决于T1 R1，因为T1 R3也是甜味刺激受体的组成部分，包括一些D-氨基酸。本研究有两个主要组成部分。首先，我将测试是否L-氨基酸和其他鲜味刺激与T1 R1的NTD相互作用，通过使用同步辐射圆二色性（SRCD）光谱和光谱荧光。其次，我将确定是否多态性T1 R1 NTD与L-谷氨酸味觉敏感性小鼠品系之间，影响T1 R结合氨基酸配体的能力。使用高度创新的方法，这些研究不仅将阐明受体结构对味觉中配体选择性的贡献，而且还将为许多氨基酸受体系统中配体-受体相互作用的结构基础提供重要见解。在我们的社会中，加工食品通常是增味的，以更吸引消费者。虽然更多的糖或谷氨酸盐（味精）可以提高食物的适口性，但过量摄入它们会导致肥胖或激素失调。了解配体与味觉受体相互作用的方式可能会导致发现没有或更少副作用的新食品添加剂。

DESCRIPTION (provided by applicant): 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.