Structure of the full-length glucagon class b g-protein-coupled receptor
文献类型：期刊论文
| 作者 | Zhang, Haonan1,2; Qiao, Anna1,2; Yang, Dehua1,3; Yang, Linlin4; Dai, Antao1,3; De Graaf, Chris5; Reedtz-Runge, Steffen; Dharmarajan, Venkatasubramanian6,7; Zhang, Hui1,2; Han, Gye Won8 |
| 刊名 | Nature
 |
| 出版日期 | 2017-06-08 |
| 卷号 | 546期号:7657页码:259-+ |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/nature22363 |
| 通讯作者 | Jiang, hualiang(hljiang@simm.ac.cn) ; Wang, ming-wei(mwwang@simm.ac.cn) ; Wu, beili(beiliwu@simm.ac.cn) |
| 英文摘要 | 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. |
| WOS关键词 | SERIAL FEMTOSECOND CRYSTALLOGRAPHY ; CORTICOTROPIN-RELEASING-FACTOR ; LIPIDIC CUBIC PHASE ; EXTRACELLULAR DOMAINS ; DRUG DISCOVERY ; BINDING-SITE ; LIGAND ; REFINEMENT ; VALIDATION ; SOFTWARE |
| WOS研究方向 | Science & Technology - Other Topics |
| WOS类目 | Multidisciplinary Sciences |
| 语种 | 英语 |
| WOS记录号 | WOS:000402823400031 |
| 出版者 | NATURE PUBLISHING GROUP |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2177346 |
| 专题 | 高能物理研究所 |
| 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 |
| 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-+. |
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