Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor

doi:10.1038/s41467-021-21030-9

	Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor
	Tang, Tingting 1,2,3; Hartig, Christin 4; Chen, Qiuru1,3,5 ; Zhao, Wenli 1,2,3; Kaiser, Anette 4; Zhang, Xuefeng 1,2,3; Zhang, Hui 1,2,3; Qu, Honge1,3,5 ; Yi, Cuiying 1; Ma, Limin 2; Han, Shuo 2; Zhao, Qiang 2,3,6,7; Beck-Sickinger, Annette G.4; Wu, Beili1,3,5,6,7
	2021-02-02
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	12 期号:1 页码:#VALUE!
DOI	10.1038/s41467-021-21030-9
摘要	The human neuropeptide Y (NPY) Y-2 receptor (Y2R) plays essential roles in food intake, bone formation and mood regulation, and has been considered an important drug target for obesity and anxiety. However, development of drugs targeting Y2R remains challenging with no success in clinical application yet. Here, we report the crystal structure of Y2R bound to a selective antagonist JNJ-31020028 at 2.8 angstrom resolution. The structure reveals molecular details of the ligand-binding mode of Y2R. Combined with mutagenesis studies, the Y2R structure provides insights into key factors that define antagonistic activity of diverse antagonists. Comparison with the previously determined antagonist-bound Y1R structures identified receptor-ligand interactions that play different roles in modulating receptor activation and mediating ligand selectivity. These findings deepen our understanding about molecular mechanisms of ligand recognition and subtype specificity of NPY receptors, and would enable structure-based drug design. The human neuropeptide Y receptor Y-2 (Y2R) is a drug target for the treatment of obesity and anxiety. Crystal structure of Y2R bound to a selective antagonist and accompanying mutagenesis provide insights into ligand recognition and subtype specificity of NPY receptors.
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收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000617063000007
出版者	NATURE RESEARCH
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125827
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_吴蓓丽组生命科学与技术学院_硕士生
通讯作者	Zhao, Qiang; Beck-Sickinger, Annette G.; Wu, Beili
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 4.Univ Leipzig, Inst Biochem, Fac Life Sci, Bruderstr 34, D-04103 Leipzig, Germany; 5.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Hua Xia Zhong Rd, Shanghai 201210, Peoples R China; 6.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Beijing 100101, Peoples R China; 7.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R 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	Tang, Tingting,Hartig, Christin,Chen, Qiuru,et al. Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor[J]. NATURE COMMUNICATIONS,2021,12(1):#VALUE!.
APA	Tang, Tingting.,Hartig, Christin.,Chen, Qiuru.,Zhao, Wenli.,Kaiser, Anette.,...&Wu, Beili.(2021).Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor.NATURE COMMUNICATIONS,12(1),#VALUE!.
MLA	Tang, Tingting,et al."Structural basis for ligand recognition of the neuropeptide Y Y-2 receptor".NATURE COMMUNICATIONS 12.1(2021):#VALUE!.