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Conformational states of the full-length glucagon receptor

文献类型：期刊论文

作者Yang, Linlin2; Yang, Dehua3,4; de Graaf, Chris1; Moeller, Arne5; West, Graham M.6; Dharmarajan, Venkatasubramanian6; Wang, Chong7; Siu, Fai Y.7; Song, Gaojie8; Reedtz-Runge, Steffen9
刊名NATURE COMMUNICATIONS
出版日期2015-07
卷号6
ISSN号2041-1723
DOI10.1038/ncomms8859
文献子类Article
英文摘要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.
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
资助项目Ministry of Science and Technology of China[2012CB518005] ; Ministry of Science and Technology of China[2012AA020302] ; Ministry of Science and Technology of China[2013ZX09507001] ; National Natural Science Foundation of China[21422208] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[91313000] ; National Natural Science Foundation of China[21210003] ; National Health and Family Planning Commission of China[2013ZX09507001] ; National Health and Family Planning Commission of China[2012ZX09304-011] ; National Health and Family Planning Commission of China[2013ZX09401003-005] ; National Health and Family Planning Commission of China[2013ZX09507-002] ; Shanghai Science and Technology Development Fund[13DZ2290300] ; Shanghai Science and Technology Development Fund[15DZ2291600] ; National Institutes of Health[U54 GM094618] ; SA-SIBS Scholarship Program[00000000] ; Thousand Talents Program in China[00000000]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000358861600005
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/276475]  
专题药物发现与设计中心
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
通讯作者Jiang, Hualiang
作者单位1.Vrije Univ Amsterdam, AIMMS, Fac Sci, Div Med Chem, NL-1081 HV Amsterdam, Netherlands;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China;
4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
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;
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).

入库方式： OAI收割

来源：上海药物研究所

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