+検索条件
-Structure paper
タイトル | Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex. |
---|---|
ジャーナル・号・ページ | Nature, Vol. 555, Issue 7694, Page 121-125, Year 2018 |
掲載日 | 2018年3月1日 |
![]() | Yi-Lynn Liang / Maryam Khoshouei / Alisa Glukhova / Sebastian G B Furness / Peishen Zhao / Lachlan Clydesdale / Cassandra Koole / Tin T Truong / David M Thal / Saifei Lei / Mazdak Radjainia / Radostin Danev / Wolfgang Baumeister / Ming-Wei Wang / Laurence J Miller / Arthur Christopoulos / Patrick M Sexton / Denise Wootten / ![]() ![]() ![]() ![]() ![]() |
PubMed 要旨 | 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. Endogenous and mimetic GLP-1 peptides exhibit biased agonism- ...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. Endogenous and mimetic GLP-1 peptides exhibit biased agonism-a difference in functional selectivity-that may provide improved therapeutic outcomes. Here we describe the structure of the human GLP-1 receptor in complex with the G protein-biased peptide exendin-P5 and a Gα heterotrimer, determined at a global resolution of 3.3 Å. 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. At the intracellular face, there was a six-degree difference in the angle of the Gαs-α5 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 Gα protein. Our structure provides insights into the molecular basis of biased agonism. |
![]() | ![]() ![]() |
手法 | EM (単粒子) |
解像度 | 3.3 Å |
構造データ | |
由来 |
|
![]() | ![]() ![]() ![]() |