G蛋白偶联受体（G protein-coupled receptors，GPCRs）是一类在细胞信号转导中发挥重要作用的膜蛋白受体家族，与人类的多种疾病密切相关。GPR119属于GPCR中的A家族受体，受体激活后与Gs蛋白偶联，促进葡萄糖依赖性胰岛素和GLP-1的分泌。GPR119是2型糖尿病的重要药物靶标，其口服型小分子激动剂是新型抗糖尿病药物研发的方向。虽然人们在GPR119的药物研发方面做了大量工作，但是对该受体的分子药理学机制认知缺乏。本课题为agonist-GPR119-Gs复合物的结构生物学研究，有助于阐明GPR119与小分子配体及Gs蛋白的识别机制，揭示GPR119的信号转导和激活机制，并为新型抗糖尿病的药物研发提供高精度的三维模板。

G-protein-coupled receptors (GPCRs) are a membrane protein family that play an important role in cellular signal transduction and are closely related to many human diseases. GPR119 belongs to class A family of GPCRs. Activated GPR119 can interact with Gs protein and promote secretion of glucose-dependent insulin and GLP-1. GPR119 is an important drug target of type 2 diabetes, and its oral small molecule agonist is a new direction of anti-diabetes drugs study. But despite massive drug discovery work in the field, very little is known about the molecular pharmacology of GPR119. This project is structure biology study of agonist-GPR119-Gs complex, which elucidates interaction mode of GPR119 with ligand and Gs, reveals its signal transduction and activation mechanism, and provides structure basis for the development of anti-diabetes drugs.