Structure of the full-length glucagon class B G-protein-coupled receptor
文献类型：期刊论文
| 作者 | Chrezov, V; Yang, HY; Hanson, MA; Stevens, RC; Zhang, HN; Dong YH(董宇辉) ; Geng Z(耿直); Wu, BL; Wang, MW; Jiang, HL
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| 刊名 | NATURE
 |
| 出版日期 | 2017 |
| 卷号 | 546期号:7657页码:259-+ |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/nature22363 |
| 文献子类 | Article |
| 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. |
| 电子版国际标准刊号 | 1476-4687 |
| 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 |
| 语种 | 英语 |
| WOS记录号 | WOS:000402823400031 |
| 源URL | [http://ir.ihep.ac.cn/handle/311005/284872]  |
| 专题 | 高能物理研究所_多学科研究中心 |
| 作者单位 | 中国科学院高能物理研究所 |
| 推荐引用方式 GB/T 7714 | Chrezov, V,Yang, HY,Hanson, MA,et al. Structure of the full-length glucagon class B G-protein-coupled receptor[J]. NATURE,2017,546(7657):259-+. |
| APA | Chrezov, V.,Yang, HY.,Hanson, MA.,Stevens, RC.,Zhang, HN.,...&Lau, J.(2017).Structure of the full-length glucagon class B G-protein-coupled receptor.NATURE,546(7657),259-+. |
| MLA | Chrezov, V,et al."Structure of the full-length glucagon class B G-protein-coupled receptor".NATURE 546.7657(2017):259-+. |
入库方式： OAI收割
来源：高能物理研究所
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