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如何特异性地与T1R味觉受体相互作用。T1R1和T1R3作为异聚体受体检测鲜味刺激，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n端结构域（NTD），这可能是配体相互作用的位点。对于T1R1:T1 R3鲜味受体，配体和受体的相互作用具有很强的选择性，它可以区分同一氨基酸的两个对映体。l -氨基酸的立体特异性依赖于T1R1，因为T1R3也是甜刺激受体的一个组成部分，包括一些d -氨基酸。这项研究有两个主要组成部分。首先，我将通过同步辐射圆二色（SRCD）光谱和荧光光谱检测l -氨基酸和其他鲜味刺激是否与T1R1的NTD相互作用。其次，我将确定与小鼠品系之间l -谷氨酸味觉敏感性相关的T1R1 NTD多态性是否会影响T1R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，加工食品通常会增强风味，以吸引消费者。虽然更多的糖或味精（MSG）可以提高食物的口感，但过量摄入会导致肥胖或荷尔蒙失调。了解配体与味觉感受器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.