Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes.
Cell Rep
; 36(2): 109374, 2021 07 13.
Article
em En
| MEDLINE
| ID: mdl-34260945
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Proteínas de Ligação ao GTP
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Complexos Multiproteicos
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Peptídeos Semelhantes ao Glucagon
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Receptor do Peptídeo Semelhante ao Glucagon 1
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article