Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor

doi:10.7554/eLife.68719

	Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor
	Zhao, Fenghui 1,2; Zhang, Chao 3,4; Zhou, Qingtong 5; Hang, Kaini 3; Zou, Xinyu 6; Chen, Yan 1,2,5; Wu, Fan 3; Rao, Qidi 3,4; Dai, Antao 7; Yin, Wanchao 2
刊名	ELIFE
	2021-07-13
卷号	10 页码:20
ISSN号	2050-084X
DOI	10.7554/eLife.68719
通讯作者	Xu, H. Eric(eric.xu@simm.ac.cn) ; Yang, Dehua(dhyang@simm.ac.cn) ; Zhao, Lihua(zhaolihuawendy@simm.ac.cn) ; Wang, Ming-Wei(mwwang@simm.ac.cn)
英文摘要	Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic target, GIPR has been subjected to intensive structural studies without success. Here, we report the cryo-EM structure of the human GIPR in complex with GIP and a G(s) heterotrimer at a global resolution of 2.9 angstrom. GIP adopts a single straight helix with its N terminus dipped into the receptor transmembrane domain (TMD), while the C terminus is closely associated with the extracellular domain and extracellular loop 1. GIPR employs conserved residues in the lower half of the TMD pocket to recognize the common segments shared by GIP homologous peptides, while uses non-conserved residues in the upper half of the TMD pocket to interact with residues specific for GIP. These results provide a structural framework of hormone recognition and GIPR activation.
资助项目	National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[32071203] ; National Natural Science Foundation of China[81773792] ; National Natural Science Foundation of China[81973373] ; National Natural Science Foundation of China[21704064] ; National Science and Technology Major Project of China[2018ZX09735-001] ; National Science and Technology Major Project of China[2018ZX09711002-002-005] ; National Key Basic Research Program of China[2018YFA0507000] ; Ministry of Science and Technology of China[2018YFA0507002] ; Shanghai Municipal Science and Technology Commission[2019SHZDZX02] ; Chinese Academy of Sciences[XDB37030103] ; Shanghai Municipality Science and Technology Development Fund[18430711500] ; Shanghai Municipality Science and Technology Development Fund[18ZR1447800] ; Novo Nordisk[NNCAS-2017-1-CC] ; Young Innovation Promotion[2018325] ; Association of the Chinese Academy of Sciences ; Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
WOS关键词	CRYO-EM STRUCTURE ; GLUCAGON RECEPTOR ; PARTIAL AGONIST ; GLP-1 RECEPTOR ; ACTIVATION ; COMPLEX ; GIP ; DYNAMICS ; PEPTIDE ; BINDING
WOS研究方向	Life Sciences & Biomedicine - Other Topics
语种	英语
出版者	ELIFE SCIENCES PUBLICATIONS LTD
WOS记录号	WOS:000677556800001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296726]
专题	中国科学院上海药物研究所
通讯作者	Xu, H. Eric; Yang, Dehua; Zhao, Lihua; Wang, Ming-Wei
作者单位	1.Fudan Univ, Sch Pharm, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai, Peoples R China 6.Huazhong Univ Sci & Technol, Sch Artificial Intelligence & Automat, Wuhan, Peoples R China 7.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai, Peoples R China 8.Zhejiang Univ, Dept Biophys, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Peoples R China 9.Zhejiang Univ, Dept Pathol, Sir Run Run Shaw Hosp, Sch Med, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Fenghui,Zhang, Chao,Zhou, Qingtong,et al. Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor[J]. ELIFE,2021,10:20.
APA	Zhao, Fenghui.,Zhang, Chao.,Zhou, Qingtong.,Hang, Kaini.,Zou, Xinyu.,...&Wang, Ming-Wei.(2021).Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor.ELIFE,10,20.
MLA	Zhao, Fenghui,et al."Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor".ELIFE 10(2021):20.