Conformational states of the full-length glucagon receptor

doi:10.1038/ncomms8859

KMS > iHuman研究所

	Conformational states of the full-length glucagon receptor
	Yang, Linlin ; Yang, Dehua ; de Graaf, Chris ; Moeller, Arne ; West, Graham M.; Dharmarajan, Venkatasubramanian ; Wang, Chong ; Siu, Fai Y.; Song, Gaojie; Reedtz-Runge, Steffen ; Pascal, Bruce D.; Wu, Beili ; Potter, Clinton S.; Zhou, Hu ; Griffin, Patrick R.; Carragher, Bridget ; Yang, Huaiyu ; Wang, Ming-Wei ; Stevens, Raymond C.; Jiang, Hualiang
	2015-07
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	6
发表状态	已发表
DOI	10.1038/ncomms8859
摘要	Class B G protein-coupled receptors are composed of an extracellular domain (ECD) and a seven-transmembrane (7TM) domain, and their signalling is regulated by peptide hormones. Using a hybrid structural biology approach together with the ECD and 7TM domain crystal structures of the glucagon receptor (GCGR), we examine the relationship between full-length receptor conformation and peptide ligand binding. Molecular dynamics (MD) and disulfide crosslinking studies suggest that apo-GCGR can adopt both an open and closed conformation associated with extensive contacts between the ECD and 7TM domain. The electron microscopy (EM) map of the full-length GCGR shows how a monoclonal antibody stabilizes the ECD and 7TM domain in an elongated conformation. Hydrogen/deuterium exchange (HDX) studies and MD simulations indicate that an open conformation is also stabilized by peptide ligand binding. The combined studies reveal the open/closed states of GCGR and suggest that glucagon binds to GCGR by a conformational selection mechanism.
收录类别	SCI
语种	英语
资助项目	National Institutes of Health[U54 GM094618]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000358861600005
出版者	NATURE PUBLISHING GROUP
WOS关键词	PROTEIN-COUPLED-RECEPTOR ; CORTICOTROPIN-RELEASING-FACTOR ; CLASS-B GPCR ; N-TERMINAL DOMAIN ; CRYSTAL-STRUCTURE ; AMINO-TERMINUS ; EXTRACELLULAR DOMAIN ; MOLECULAR RECOGNITION ; ELECTRON-MICROSCOPY ; MUTATIONAL ANALYSIS
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/2184
专题	iHuman研究所 iHuman研究所_特聘教授组_Raymond Stevens组 iHuman研究所_PI研究组_刘志杰组
通讯作者	Jiang, Hualiang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 4.Vrije Univ Amsterdam, AIMMS, Fac Sci, Div Med Chem, NL-1081 HV Amsterdam, Netherlands 5.Scripps Res Inst, Natl Resource Automated Mol Microscopy, La Jolla, CA 92037 USA 6.Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA 7.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA 8.ShanghaiTech Univ, iHuman Inst, Shanghai 201203, Peoples R China 9.Novo Nordisk AS, Dept Modeling & Struct Biol, DK-2760 Malov, Denmark 10.Univ So Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA 90089 USA 11.Univ So Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA
推荐引用方式 GB/T 7714	Yang, Linlin,Yang, Dehua,de Graaf, Chris,et al. Conformational states of the full-length glucagon receptor[J]. NATURE COMMUNICATIONS,2015,6.
APA	Yang, Linlin.,Yang, Dehua.,de Graaf, Chris.,Moeller, Arne.,West, Graham M..,...&Jiang, Hualiang.(2015).Conformational states of the full-length glucagon receptor.NATURE COMMUNICATIONS,6.
MLA	Yang, Linlin,et al."Conformational states of the full-length glucagon receptor".NATURE COMMUNICATIONS 6(2015).