期刊
NATURE
卷 555, 期 7694, 页码 121-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature25773
关键词
-
资金
- Monash University Ramaciotti Centre for Cryo-Electron Microscopy
- National Health and Medical Research Council of Australia (NHMRC) [1061044, 1065410, 1120919, 1126857]
- NHMRC [1055134]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12020347]
- Shanghai Science and Technology Development Fund [15DZ2291600]
- CAS
The class B glucagon-like peptide-1 (GLP-1) G protein-coupled receptor is a major target for the treatment of type 2 diabetes and obesity(1). Endogenous and mimetic GLP-1 peptides exhibit biased agonism-a difference in functional selectivity-that may provide improved therapeutic outcomes1. Here we describe the structure of the human GLP-1 receptor in complex with the G protein-biased peptide exendin-P5 and a G alpha(s) heterotrimer, determined at a global resolution of 3.3 angstrom. At the extracellular surface, the organization of extracellular loop 3 and proximal transmembrane segments differs between our exendin-P5-bound structure and previous GLP-1-bound GLP-1 receptor structure(2). At the intracellular face, there was a six-degree difference in the angle of the G alpha(s)-alpha 5 helix engagement between structures, which was propagated across the G protein heterotrimer. In addition, the structures differed in the rate and extent of conformational reorganization of the G alpha(s) protein. Our structure provides insights into the molecular basis of biased agonism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据