Full-length human GLP-1 receptor structure without orthosteric ligands
文献类型：期刊论文
| 作者 | Fan Wu; Linlin Yang; Kaini Hang; Mette Laursen; Lijie Wu; Gye Won Han; Qiansheng Ren; Nikolaj Kulahin Roed; Guangyao Lin; Michael A. Hanson |
| 刊名 | naturecommunications
 |
| 出版日期 | 2020 |
| 卷号 | 11期号:1页码:1 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-020-14934-5 |
| 英文摘要 | Glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor that plays an important role in glucose homeostasis and treatment of type 2 diabetes. Structures of full-length class B receptors were determined in complex with their orthosteric agonist peptides, however, little is known about their extracellular domain (ECD) conformations in the absence of orthosteric ligands, which has limited our understanding of their activation mechanism. Here, we report the 3.2?? resolution, peptide-free crystal structure of the full-length human GLP-1R in an inactive state, which reveals a unique closed conformation of the ECD. Disulfide cross-linking validates the physiological relevance of the closed conformation, while electron microscopy (EM) and molecular dynamic (MD) simulations suggest a large degree of conformational dynamics of ECD that is necessary for binding GLP-1. Our inactive structure represents a snapshot of the peptide-free GLP-1R and provides insights into the activation pathway of this receptor family. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280414]  |
| 专题 | 新药研究国家重点实验室 |
| 作者单位 | 1.GPCR Consortium 2.Shanghai Institute of Materia Medica, Chinese Academy of Sciences 3.Shanghai Institute of Materia Medica, Chinese Academy of Sciences 4.Shanghai Institute of Materia Medica, Chinese Academy of Sciences 5.East China Normal University 6.Fudan University 7.Shanghai Institute of Materia Medica, Chinese Academy of Sciences 8.ShanghaiTech University 9.ShanghaiTech University 10.University of Chinese Academy of Sciences |
| 推荐引用方式 GB/T 7714 | Fan Wu,Linlin Yang,Kaini Hang,et al. Full-length human GLP-1 receptor structure without orthosteric ligands[J]. naturecommunications,2020,11(1):1. |
| APA | Fan Wu.,Linlin Yang.,Kaini Hang.,Mette Laursen.,Lijie Wu.,...&Raymond C. Stevens.(2020).Full-length human GLP-1 receptor structure without orthosteric ligands.naturecommunications,11(1),1. |
| MLA | Fan Wu,et al."Full-length human GLP-1 receptor structure without orthosteric ligands".naturecommunications 11.1(2020):1. |
入库方式： OAI收割
来源：上海药物研究所
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