Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors

doi:10.1038/s41467-022-29072-3

	Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors
	Duan, Jia 1,2; Shen, Dan Dan 3; Zhao, Tingting 4,5; Guo, Shimeng 4,5; He, Xinheng 1,2; Yin, Wanchao 1; Xu, Peiyu 1; Ji, Yujie 1,2; Chen, Li Nan 3; Liu, Jinyu 4,5; Zhang, Huibing 3; Liu, Qiufeng 1; Shi, Yi 1; Cheng, Xi 1; Jiang, Hualiang1,2,6 ; Eric Xu, H.1,2,6 ; Zhang, Yan 3,7,8,9; Xie, Xin 1,4,5,10,11; Jiang, Yi1,6,12
	2022-03-15
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	13 期号:1
发表状态	已发表
DOI	10.1038/s41467-022-29072-3
摘要	Peptide hormones and neuropeptides are complex signaling molecules that predominately function through G protein-coupled receptors (GPCRs). Two unanswered questions remaining in the field of peptide-GPCR signaling systems pertain to the basis for the diverse binding modes of peptide ligands and the specificity of G protein coupling. Here, we report the structures of a neuropeptide, galanin, bound to its receptors, GAL1R and GAL2R, in complex with their primary G protein subtypes G and G, respectively. The structures reveal a unique binding pose of galanin, which almost ‘lays flat’ on the top of the receptor transmembrane domain pocket in an α-helical conformation, and acts as an ‘allosteric-like’ agonist via a distinct signal transduction cascade. The structures also uncover the important features of intracellular loop 2 (ICL2) that mediate specific interactions with G, thus determining the selective coupling of G to GAL2R. ICL2 replacement in G-coupled GAL1R, μOR, 5-HTR, and G-coupled βAR and D1R with that of GAL2R promotes G coupling of these receptors, highlighting the dominant roles of ICL2 in G selectivity. Together our results provide insights into peptide ligand recognition and allosteric activation of galanin receptors and uncover a general structural element for G coupling selectivity.
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收录类别	SCIE
语种	英语
Scopus 记录号	2-s2.0-85126511043
来源库	Scopus
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/165033
专题	免疫化学研究所_特聘教授组_蒋华良组生命科学与技术学院生命科学与技术学院_特聘教授组_徐华强组
通讯作者	Eric Xu, H.; Zhang, Yan; Xie, Xin; Jiang, Yi
作者单位	1.CAS Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China 2.University of Chinese Academy of Sciences,Beijing,100049,China 3.Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang,China 4.School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing,210046,China 5.CAS Key Laboratory of Receptor Research,National Center for Drug Screening,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China 6.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China 7.Liangzhu Laboratory,Zhejiang University Medical Center,Hangzhou,Zhejiang,China 8.MOE Frontier Science Center for Brain Research and Brain-Machine Integration,Zhejiang University School of Medicine,Hangzhou,Zhejiang,China 9.Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province,Hangzhou,Zhejiang,China 10.State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China 11.School of Pharmaceutical Science and Technology,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou,310024,China 12.Lingang Laboratory,Shanghai,200031,China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Duan, Jia,Shen, Dan Dan,Zhao, Tingting,et al. Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors[J]. NATURE COMMUNICATIONS,2022,13(1).
APA	Duan, Jia.,Shen, Dan Dan.,Zhao, Tingting.,Guo, Shimeng.,He, Xinheng.,...&Jiang, Yi.(2022).Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors.NATURE COMMUNICATIONS,13(1).
MLA	Duan, Jia,et al."Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors".NATURE COMMUNICATIONS 13.1(2022).