Structure of the full-length glucagon class B G-protein-coupled receptor

doi:10.1038/nature22363

KMS > iHuman研究所

	Structure of the full-length glucagon class B G-protein-coupled receptor
	Zhang, Haonan 1,2; Qiao, Anna 1,2; Yang, Dehua 1,3; Yang, Linlin 4; Dai, Antao 1,3; De Graaf, Chris 5; Reedtz-Runge, Steffen ; Dharmarajan, Venkatasubramanian 6,7; Zhang, Hui 1,2; Han, Gye Won 8; Grant, Thomas D.9; Sierra, Raymond G.10; Weierstall, Uwe 11; Nelson, Garrett 11; Liu, Wei 12; Wu, Yanhong1,2,13 ; Ma, Limin 1; Cai, Xiaoqing 1,3; Lin, Guangyao1,2,3,13 ; Wu, Xiaoai 14; Geng, Zhi 15; Dong, Yuhui 15; Song, Gaojie16 ; Griffin, Patrick R.7; Lau, Jesper 6; Chrezov, Vadim 8; Yang, Huaiyu 17; Hanson, Michael A.18; Stevens, Raymond C.13,16 ; Zhao, Qiang 1,2,19,20; Jiang, Hualiang1,17,19 ; Wang, Ming-Wei1,3,13,21 ; Wu, Beili1,2,13,20
	2017-06-08
发表期刊	NATURE (IF:50.5[JCR-2023],54.4[5-Year])
ISSN	0028-0836
卷号	546 期号:7657 页码:259-+
发表状态	已发表
DOI	10.1038/nature22363
摘要	The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled receptor family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 angstrom crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation. The two domains are connected by a 12-residue segment termed the stalk, which adopts a beta-strand conformation, instead of forming an alpha-helix as observed in the previously solved structure of the GCGR transmembrane domain. The first extracellular loop exhibits a beta-hairpin conformation and interacts with the stalk to form a compact beta-sheet structure. Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics studies suggest that the stalk and the first extracellular loop have critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding of the signalling mechanisms of class B G-protein-coupled receptors.
收录类别	SCI
语种	英语
资助项目	US Department of Energy, Office of Science, Office of Basic Energy Sciences[DE-AC02-76SF00515]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000402823400031
出版者	NATURE PUBLISHING GROUP
WOS关键词	SERIAL FEMTOSECOND CRYSTALLOGRAPHY ; CORTICOTROPIN-RELEASING-FACTOR ; LIPIDIC CUBIC PHASE ; EXTRACELLULAR DOMAINS ; DRUG DISCOVERY ; BINDING-SITE ; LIGAND ; REFINEMENT ; VALIDATION ; SOFTWARE
原始文献类型	Article
通讯作者	Jiang, Hualiang ; Wang, Ming-Wei ; Wu, Beili
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/1336
专题	iHuman研究所生命科学与技术学院 iHuman研究所_特聘教授组_Raymond Stevens组生命科学与技术学院_特聘教授组_王明伟组生命科学与技术学院_特聘教授组_吴蓓丽组免疫化学研究所_特聘教授组_蒋华良组 iHuman研究所_PI研究组_刘志杰组生命科学与技术学院_博士生
通讯作者	Jiang, Hualiang; Wang, Ming-Wei; 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.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, 189 Guo Shou Jing Rd, Shanghai 201203, Peoples R China 4.Zhengzhou Univ, Sch Basic Med Sci, Dept Pharmacol, 100 Sci Ave, Zhengzhou 450001, Peoples R China 5.Vrije Univ Amsterdam, AIMMS, Fac Sci, Div Med Chem, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands 6.Novo Nordisk AS, Novo Nordisk Pk, DK-2760 Malov, Denmark 7.Scripps Res Inst, Dept Mol Med, 130 Scripps Way, Jupiter, FL 33458 USA 8.Univ Southern Calif, Dept Chem, Bridge Inst, 3430 S Vermont Ave, Los Angeles, CA 90089 USA 9.SUNY Buffalo, Hauptman Woodward Inst, 700 Ellicott St, Buffalo, NY 14203 USA 10.SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA 11.Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA 12.Arizona State Univ, Biodesign Inst, Sch Mol Sci, Biodesign Ctr Appl Struct Discovery, Tempe, AZ 85287 USA 13.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Hua Xia Zhong Rd, Shanghai 201210, Peoples R China 14.Novo Nordisk Res Ctr China, 20 Life Sci Pk Rd, Beijing 102206, Peoples R China 15.Chinese Acad Sci, Beijing Synchrotron Radiat Facil, Inst High Energy Phys, Beijing 100049, Peoples R China 16.ShanghaiTech Univ, iHuman Inst, 393 Hua Xia Zhong Rd, Shanghai 201210, Peoples R China 17.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 18.GPCR Consortium, San Marcos, CA 92078 USA 19.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 20.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Beijing 100101, Peoples R China 21.Fudan Univ, Sch Pharm, 826 Zhangheng Rd, Shanghai 201203, 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	Zhang, Haonan,Qiao, Anna,Yang, Dehua,et al. Structure of the full-length glucagon class B G-protein-coupled receptor[J]. NATURE,2017,546(7657):259-+.
APA	Zhang, Haonan.,Qiao, Anna.,Yang, Dehua.,Yang, Linlin.,Dai, Antao.,...&Wu, Beili.(2017).Structure of the full-length glucagon class B G-protein-coupled receptor.NATURE,546(7657),259-+.
MLA	Zhang, Haonan,et al."Structure of the full-length glucagon class B G-protein-coupled receptor".NATURE 546.7657(2017):259-+.