GPCR二聚体结构及功能  

Structure and Function of GPCR Dimer

作　　者：李传宝 黎晨卉 薛礼 LI Chuan-Bao;LI Chen-Hui;XUE Li(Department of Neurosurgery,Center of Pituitary Tumor,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;School of Biotechnology,East China University of Science and Technology,Shanghai 200237,China;Medical School,Kunming University of Science and Technology,Kunming 650500,China)

机构地区：[1]上海交通大学医学院附属瑞金医院神经外科,泌乳素诊治中心,上海200025 [2]华东理工大学生物工程学院,上海200237 [3]昆明理工大学医学院,昆明650500

出　　处：《生物化学与生物物理进展》2024年第11期2787-2804,共18页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(82172605)资助项目。

摘　　要：G蛋白偶联受体(G-protein coupled receptor,GPCR)是最广泛表达的膜蛋白家族之一,其可接收胞外信号刺激,通过自身构象变化激活胞内G蛋白等一系列信号通路,参与众多生理调节过程,具有重要的功能,因此其也是重要的药物靶点。GPCR二聚化是调控其功能的重要形式之一,靶向GPCR二聚体开发药物是药物研发的一个新方向。越来越多的研究报道了GPCR二聚化及其结构与功能调控的机制,本文综述了GPCR二聚体结构及功能的研究进展,为了解GPCR二聚体的发现、二聚化方式、功能调控机制,及进一步靶向GPCR二聚体药物开发提供了研究基础。G-protein coupled receptors(GPCRs)are an essential family of proteins on the cell membrane,widely distributed in various types of tissues and cells.Typical GPCRs are composed of characteristic 7 transmembraneα-helix domains,extracellular domain and intracellular domain.They play a key role in transmitting information inside and outside cells.These receptors can sense and respond to a variety of external signals,including odor molecules,hormones,neurotransmitters,chemokines,and so on,thereby regulating the physiological functions and metabolic activities of cells.When external signal molecules bind,these receptors undergo conformational changes,thereby activating signal transduction pathways inside cells.The most common downstream signal pathway is the activation of G proteins,but it may also activate theβ-arrestin signaling pathway.This series of signal transduction processes ultimately regulates physiological processes such as cell metabolism,proliferation,and differentiation,and also plays an important role in the occurrence and development of diseases.Due to its importance in regulating cell functions and participating in the development of diseases,GPCRs have become important targets in the field of drug research and development.The mechanism of action of many drugs is achieved by intervening in the GPCR signaling pathway.As important form of function regulating,dimerization has attracted widespread attention in the research of GPCR field.In the early days,the formation of GPCR dimerization and its effect on receptor function were mainly studied by immunoprecipitation,immunofluorescence and radioligand binding experiments in overexpression systems.Nowadays,with the continuous development of biochemical and biophysical methods,more and more GPCR dimers have been identified.GPCR dimer refers to the process in which two GPCR subunits bind to each other to form a complex.The same GPCR subunits form homodimers,and different GPCR subunits form heterodimers through direct interaction.Dimerization changes the activ

关 键 词：G蛋白偶联受体 二聚体 GPCR二聚体结构 GPCR二聚体功能 

分 类 号：Q2[生物学—细胞生物学] Q6