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-Structure paper
タイトル | Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes. |
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ジャーナル・号・ページ | Cell Rep, Vol. 36, Issue 2, Page 109374, Year 2021 |
掲載日 | 2021年7月13日 |
著者 | Xin Zhang / Matthew J Belousoff / Yi-Lynn Liang / Radostin Danev / Patrick M Sexton / Denise Wootten / |
PubMed 要旨 | The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism, and appetite and is an important target for treatment of type 2 diabetes and obesity. Multiple GLP- ...The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism, and appetite and is an important target for treatment of type 2 diabetes and obesity. Multiple GLP-1R agonists have entered into clinical trials, with some, such as semaglutide, progressing to approval. Others, including taspoglutide, failed due to the high incidence of side effects or insufficient efficacy. GLP-1R agonists have a broad spectrum of signaling profiles, but molecular understanding is limited by a lack of structural information on how different agonists engage with the GLP-1R. Here, we report cryoelectron microscopy (cryo-EM) structures and cryo-EM 3D variability analysis of semaglutide- and taspoglutide-bound GLP-1R-Gs protein complexes. These reveal similar peptide interactions to GLP-1 but different motions within the receptor and bound peptides, providing insights into the molecular determinants of GLP-1R peptide engagement. |
リンク | Cell Rep / PubMed:34260945 |
手法 | EM (単粒子) |
解像度 | 2.5 Å |
構造データ | EMDB-22882, PDB-7ki0: EMDB-22883, PDB-7ki1: |
化合物 | ChemComp-WF1: ChemComp-HOH: |
由来 |
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キーワード | MEMBRANE PROTEIN / Glucagon-Like peptide-1 (GLP-1) Receptor semaglutide cryoEM / Glucagon-Like peptide-1 (GLP-1) Receptor / taspoglutide |