G蛋白偶联受体（GPCR）是重要的跨膜信号传导蛋白，超过50%的药物以GPCR为靶点。GPCR进行跨膜信号传递时其结构是动态变化的，具有多种不同的构象，其结构、动态构象变化信息是药物开发和筛选的重要依据。C家族受体形成二聚体、分子量大、表达纯化困难，目前其结构和构象变化信息知之甚少。GPRC6A受体是C家族成员，在前列腺癌、炎症反应、骨矿化和男性生殖等生理和病理过程起关键作用，但至今仍没有GPRC6A受体的结构和动态构象变化报道。本项目将应用单颗粒冷冻电镜方法解析GPRC6A受体静息及激活状态下的三维结构；并应用19F定点标记以及19F核磁共振方法分析不同类型配体结合GPRC6A受体的动态构象变化和动力学，加深对GPRC6A受体信号传导的分子机制和下游信号选择性的理解和阐释，为药物开发和筛选提供重要的结构信息和设计指导，同时加深对C家族GPCR受体信号转导及构象变化过程的理解。

G protein-coupled receptors (GPCRs) are important transmembrane signaling proteins, with more than 50% of drugs targeting GPCRs. GPCR has a dynamic structure when it transmits extracellular stimulation. Studying of its structure and dynamic conformational change is an important basis for drug development and screening. Resolved structure of class C receptors is more difficult because the dimerization of receptors and difficult to expression and purification. GPRC6A (GPCR, class C, group 6, subtype A) is a class C GPCR that play important role in physiological and pathological processes such as prostate cancer, in inflammation, bone metabolism and male reproduction. To study the molecular mechanism of tansmembrane signal transduction of GPRC6A, the resting and activated structures of GPRC6A will be resolved by cryo-electron microscopy (cryo‑EM). Futhermore, dynamic conformational change of GPRC6A will be investigated by 19F site-specific labeling and 19F nuclear magnetic resonance (NMR). It will provides structural information and dynamic support for the discovery of new drugs. At the same time, signal transduction mechanism of the class C receptor was improved.