The structural basis of L-amino acid taste

L-氨基酸味道的结构基础

• 批准号: 7409048
• 负责人: Stephan Vigues
• 金额: $ 7.21万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7409048
• 关键词: Adverse effects; Affect; Agonist; Amino Acid Receptors; Amino Acids; Animals; Behavioral; Binding; Biology; Cells; Chemicals; Circular Dichroism; Circular Dichroism Spectroscopy; Class; Cues; Cyclamates; Detection; Endocrine; Engineering; Environment; Event; Exhibits; Family; Flavoring; Fluorescence; Fluorescence Spectroscopy; Food; Food Additives; Food Processing; G-Protein-Coupled Receptors; Genetic Polymorphism; Glutamates; Goals; Hormonal; Hypothalamic structure; Ingestion; Japanese Population; Lead; Ligand Binding; Ligands; Metabotropic Glutamate Receptors; Molecular Conformation; Mouse Strains; Mus; N-terminal; Numbers; Obesity; Organism; Perception; Phenotype; Proteins; Radiation; Receptor Cell; Regulation; Reproduction; Rodent; Role; Sensory; Site; Societies; Sodium Glutamate; Specificity; Stimulus; Structure; Sweetening Agents; System; T1R receptor; Taste Perception; Testing; Transmembrane Domain; Tryptophan; Venus Flytrap; base; desire; enantiomer; extracellular; feeding; innovation; insight; lipophilicity; member; molecular size; receptor; response; sugar; sweet receptor; sweet taste perception; synchrotron radiation

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.

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与 T1R 味觉受体特异性相互作用。 T1R1 和 T1R3 作为异聚受体来检测 L-氨基酸等鲜味刺激。两个亚基均属于 C 类 GPCR 家族，其成员具有长的 N 末端结构域 (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选择性，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 T1R1，因为 T1R3 也是甜味刺激受体的组成部分，包括一些 D-氨基酸。这项研究有两个主要组成部分。首先，我将使用同步辐射圆二色性 (SRCD) 光谱和分光荧光来测试 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 T1R1 NTD 中与小鼠品系之间 L-谷氨酸味觉敏感性相关的多态性是否会影响 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，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的见解。我们社会中提供的加工食品通常经过风味增强，以对消费者更具吸引力。虽然更多的糖或味精 (MSG) 可以增强食物的适口性，但过量摄入会导致肥胖或荷尔蒙失调。了解配体与味觉受体相互作用的方式可能有助于发现没有或更少副作用的新食品添加剂。