N-glycosylation of the beta(2) adrenergic receptor regulates receptor function by modulating dimerization

doi:10.1111/febs.14098

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	N-glycosylation of the beta(2) adrenergic receptor regulates receptor function by modulating dimerization
	Li, Xiaona 1,2; Zhou, Mang 3; Huang, Wei 3; Yang, Huaiyu 1,4
刊名	FEBS JOURNAL
	2017-07
卷号	284 期号:13 页码:2004-2018
关键词	adrenergic receptor dimerization function G-protein-coupled receptor N-glycosylation
ISSN号	1742-464X
DOI	10.1111/febs.14098
文献子类	Article
英文摘要	N-glycosylation is a common post-translational modification of G-protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. beta(2) adrenergic receptor (beta(2)AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus, and Asn187 at the second extracellular loop (ECL2). Here, we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G-protein-dependent signaling, barrestin2 recruitment, and receptor internalization. Both N6Q and N15Q showed decreased receptor dimerization, while N187Q did not influence receptor dimerization. As decreased beta(2)AR homodimer accompanied with reduced efficiency for receptor function, we proposed that the N-glycosylation of beta(2)AR regulated receptor function by influencing receptor dimerization. To verify this hypothesis, we further paid attention to the residues at the dimerization interface. Studies of Lys60 and Glu338, two residues at the receptor dimerization interface, exhibited that the K60A/E338A showed decreased beta(2)AR dimerization and its effects on receptor signaling were similar to N6Q and N15Q, which further supported the importance of receptor dimerization for receptor function. This work provides new insights into the relationship among glycosylation, dimerization, and function of GPCRs.
资助项目	Ministry of Science and Technology of China[2012CB518005] ; Ministry of Science and Technology of China[2015CB910304] ; National Natural Science Foundation of China[21422208] ; National Natural Science Foundation of China[21372238] ; National Natural Science Foundation of China[21572244] ; E-Institutes of Shanghai Municipal Education Commission[E09013] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[00000000]
WOS关键词	PROTEIN-COUPLED RECEPTORS ; RESONANCE ENERGY-TRANSFER ; BETA(2)-ADRENERGIC RECEPTOR ; CELL-SURFACE ; CRYSTAL-STRUCTURE ; LIGAND-BINDING ; BETA-2-ADRENERGIC RECEPTOR ; SIGNAL-TRANSDUCTION ; ARRESTIN ; ACTIVATION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	WILEY
WOS记录号	WOS:000404720700006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272591]
专题	生物技术药物研发中心（筹）中科院受体结构与功能重点实验室新药研究国家重点实验室药物安全性评价中心
通讯作者	Huang, Wei; Yang, Huaiyu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Beijing, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Shanghai Univ E Inst Chem Biol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Li, Xiaona,Zhou, Mang,Huang, Wei,et al. N-glycosylation of the beta(2) adrenergic receptor regulates receptor function by modulating dimerization[J]. FEBS JOURNAL,2017,284(13):2004-2018.
APA	Li, Xiaona,Zhou, Mang,Huang, Wei,&Yang, Huaiyu.(2017).N-glycosylation of the beta(2) adrenergic receptor regulates receptor function by modulating dimerization.FEBS JOURNAL,284(13),2004-2018.
MLA	Li, Xiaona,et al."N-glycosylation of the beta(2) adrenergic receptor regulates receptor function by modulating dimerization".FEBS JOURNAL 284.13(2017):2004-2018.