G蛋白偶联受体的化学动态修饰和化学干预  

Dynamic chemical modifications and chemical interventions of G protein-coupled receptor

作　　者：徐萍 胡骏驰[3] 高玉婷 文鑫 曹玉婷 郭祖奉 易文 杨帆 李亦舟 党永军 张岩 Ping Xu;Jun-Chi Hu;Yu-Ting Gao;Xin Wen;Yu-Ting Cao;Zu-Feng Guo;Wen Yi;Fan Yang;Yi-Zhou Li;Yong-Jun Dang;Yan Zhang(Institute of Cytology and Genetics,School of Basic Medical Sciences,Hengyang Medical School,University of South China,Hengyang 421001,China;School of Basic Medical Sciences,Zhejiang University,Hangzhou 310012,China;Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention,Ministry of Education,Chongqing Medical University,Chongqing 400016,China;Innovative Drug Research Center,School of Pharmaceutical Sciences,Chongqing University,Chongqing 401331,China;School of Basic Medical Sciences,Shandong University,Jinan 250012,China;College of Life Sciences,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]南华大学,衡阳医学院,基础医学院,细胞与遗传研究所,衡阳421001 [2]浙江大学基础医学院,杭州310012 [3]重庆医科大学,新靶标与化学干预教育部医药基础研究创新中心,重庆400016 [4]重庆大学药学院,创新药物研究中心,重庆401331 [5]山东大学基础医学院,济南250012 [6]浙江大学生命科学学院,杭州310058

出　　处：《中国科学:化学》2025年第4期877-891,共15页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:92353303)资助项目。

摘　　要：G蛋白偶联受体(GPCR)在细胞信号转导中发挥关键核心作用,其功能通过多种化学修饰精细调控.本文综述了GPCR的主要化学修饰类型,包括磷酸化、糖基化、泛素化和棕榈酰化,并探讨了这些修饰如何影响受体的活性、稳定性、膜定位及信号转导.特别是,磷酸化修饰通过G蛋白偶联受体激酶(GRKs)调控β-Arrestin的结合,进而调节信号转导的强度和持续时间.糖基化修饰影响受体的膜表面表达以及信号偏向性,而泛素化与棕榈酰化修饰则涉及受体的降解、内吞以及膜定位的调控.本文还探讨了这些化学修饰在药物开发中的潜在应用,特别是在心血管疾病、神经退行性疾病和代谢紊乱等领域的最新研究进展,为未来药物设计提供了新的策略和视角.最后,本文总结了GPCR修饰研究在生物学和临床应用中的前景与挑战.G protein-coupled receptor(GPCR)plays a key role in cell signal transduction,and its function is finely regulated by a variety of chemical modifications.This article reviews the main types of chemical modifications of GPCR,including phosphorylation,glycosylation,ubiquitination,and palmitoylation,and discusses how these modifications affect receptor activity,stability,membrane localization,and signal transduction.In particular,phosphorylation of GPCR via G protein-coupled receptor kinases(GRKs)regulates the binding of β-Arrestin,thereby regulating the strength and duration of signal transduction.Glycosylation modification affects the membrane surface expression and signal bias of the receptor,while ubiquitination and palmitoylation modifications involve the regulation of receptor degradation,endocytosis and membrane localization.This paper also discusses the potential applications of these chemical modifications of GPCR in drug development,especially the recent research progress in the fields of cardiovascular diseases,neurodegenerative diseases and metabolic disorders,providing new strategies and perspectives for future drug design.Finally,this paper summarizes the prospects and challenges of GPCR modification research in biology and clinical applications.

关 键 词：G蛋白偶联受体 化学修饰 磷酸化 糖基化 化学干预 

分 类 号：R363[医药卫生—病理学]