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G蛋白偶联受体(GPCR)是细胞膜上最大的一类受体,其通过构象变化激活下游G蛋白从而介导细胞响应多种来自内源和外界环境中的信号。自GPCR被发现以来,研究者就一直在努力解析GPCR的构象,x射线晶体衍射技术和GPCR蛋白质结晶技术的发展使得越来越多的GPCR单体在静息状态,以及与不同配体甚至G蛋白结合的晶体结构被成功解析。另一方面,FRET和电子显微技术的运用得到了GPCR二聚化和多聚化的多方面证据。本文将结合近年来该领域的进展,对GPCR寡聚体的结构和构象变化予以系统的综述,这些成果为研究GPCR的功能机制及其特异性的靶点药物开发提供了重要的基础。
G-protein coupled receptors (GPCRs) are the largest class of receptors on the cell membrane that activate downstream G proteins through conformational changes to mediate cellular responses to a variety of signals from the endogenous and exogenous environment. Since the discovery of GPCR, researchers have been trying hard to resolve the conformation of GPCR. The development of x-ray crystallography and GPCR protein crystallography has led to the increasing number of GPCR monomers at rest, as well as their interaction with different ligands and even G The protein-bound crystal structure was successfully resolved. On the other hand, the use of FRET and electron microscopy has led to extensive evidence of dimerization and multimerization of GPCRs. In this paper, we will systematically review the structure and conformational changes of GPCR oligomers based on the progress in this field in recent years. These results provide an important basis for studying the functional mechanism of GPCR and the development of specific target drugs.