甜味蛋白质大分子味觉感知及其激活甜味受体-G蛋白偶联受体（GPCR）T1R2/3的分子机制

项目名称： 甜味蛋白质大分子味觉感知及其激活甜味受体-G蛋白偶联受体（GPCR）T1R2/3的分子机制

项目编号： No.31271118

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 刘波

作者单位： 齐鲁工业大学

项目金额： 76万元

中文摘要： G蛋白偶联受体（GPCR）是哺乳动物细胞最重要的一类膜蛋白并介导绝大多数外界环境信号的刺激与感应。甜味类化合物与C家族GPCR-异二聚体T1R2/T1R3相互作用, 从而激活受体并引起甜味觉的感知。虽然小分子甜味剂激活甜味受体的机制已有较多报道，对于大分子及空间体积的甜味蛋白质如何激活受体尚不清楚。本研究将首次以序列相似性高但对甜味蛋白质monellin、thaumatin等具有不同反应的人及squirrel monkey (松鼠猴) T1R2/3受体为研究对象，综合运用嵌合体及突变体、分子建模、钙离子成像等技术方法，鉴定甜味蛋白在受体上的结合位点，提出甜味蛋白质大分子与T1R2/3受体相互作用的结构模型，阐明甜味蛋白质大分子激活甜味受体T1R2/3的分子机制。研究结果对于我们理解GPCR的结构与功能以及甜味觉形成的机理具有重要意义。

中文关键词： 甜味蛋白质；甜味受体；G蛋白偶联受体；结构；分子机制

英文摘要： G protein coupled receptor (GPCR) is the most important membrane protein family in mammalian which mediates the stimulation and response towards the majority of outside environmental signals. Sweetener compounds interact with C family GPCR-heterodimeric TR2/TR3, and then activate the receptor which induces the sense of sweet taste. Although the activation mechanism of sweet receptors by small molecular sweeteners have been well reported, how the sweet proteins with macromolecular weight and steric conformation activate the receptor remains elusive. In this study, the functions of sweet receptors-human and squirrel monkey T1R2/3 receptors which have high sequence identity but distinct responses towards sweet proteins monellin and thaumatin were investigated. By use of chimeras and mutants, molecular modeling, calcium image etc, the binding site of sweet proteins on the receptors was identified, the structural model of the interaction between sweet proteins and TR2/3 receptor was suggested, and the molecular mechanism of sweet receptors activation by sweet taste proteins was elucidated. This study is meaningful for us to understand the relationship between structure and function of GPCR, as well as the inductive mechanism of sweet taste sense.

英文关键词： sweet-tasting proteins；sweet receptor；G-protein coupled receptor；structure；molecular mechanism