دورية أكاديمية
Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes
العنوان: | Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes |
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المؤلفون: | Xin Zhang, Matthew J. Belousoff, Yi-Lynn Liang, Radostin Danev, Patrick M. Sexton, Denise Wootten |
المصدر: | Cell Reports, Vol 36, Iss 2, Pp 109374- (2021) |
بيانات النشر: | Elsevier, 2021. |
سنة النشر: | 2021 |
المجموعة: | LCC:Biology (General) |
مصطلحات موضوعية: | glucagon-like peptide-1 receptor, GLP-1R, cryoelectron microscopy, GPCRs, GPCR dynamics, semaglutide, Biology (General), QH301-705.5 |
الوصف: | Summary: 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2211-1247 |
العلاقة: | http://www.sciencedirect.com/science/article/pii/S2211124721007725Test; https://doaj.org/toc/2211-1247Test |
DOI: | 10.1016/j.celrep.2021.109374 |
الوصول الحر: | https://doaj.org/article/98a1b8a90b1f44578c7736121c0ec9c6Test |
رقم الانضمام: | edsdoj.98a1b8a90b1f44578c7736121c0ec9c6 |
قاعدة البيانات: | Directory of Open Access Journals |