G蛋白偶联受体（G protein-coupled receptor, GPCR）是参与细胞表面信号传导的一类重要膜受体，也是很多上市药物的作用靶点。其中一类粘附型GPCR广泛参与细胞粘附、细胞免疫、细胞炎症以及癌症发生等。粘附型GPCR兼具有胞外的粘附结构域、GAIN结构域以及典型七次跨膜区和胞内域。胞外域结合配体的信号通过七次跨膜区传递到胞内，但目前为止我们还不知道胞外域是如何联系到跨膜区，以及配体结合信号是如何传递到跨膜区。本课题综合利用生物物理学方法，了解粘附结构域与配体的结合方式，GAIN结构域去折叠动力学，以及尝试获得跨膜区的多种构型以揭示其活化过程。该研究将弥补GPCR家族蛋白活化机理上的缺失，并且为针对粘附型GPCR结构的小分子药物设计奠定坚实基础。

G protein-coupled receptor (GPCR) is a family of receptors that involved in signal transduction across the cell membrane, as well as targets of many drugs on the market. One subfamily of GPCR, adhesion GPCR, participates in the function of cell adhesion, cell immunology, inflammation and cancer. Adhesion GPCR includes variable tandem adhesion domains followed by a common GAIN domain in the extracellular region, and then a typical transmembrane domain and a cytoplasmic tail. So far we do not know how the extracellular region is connected to the transmembrane domain, and how the signal of ligand binding in the extracellular region is transmitted to the cytoplasmic tail. We will use comprehensive biophysics methods to study the binding mode of ligand-receptor, the unfolding dynamic and mechanism of GAIN domain, as well as multiple conformations of the transmembrane domain. These study will not only help us to understand the signaling mechanism of adhesion subfamily of GPCR, but also pave the way for the development of small molecule drugs targeting the adhesion GPCR subfamily.