7KI0
Semaglutide-bound Glucagon-Like Peptide-1 (GLP-1) Receptor in Complex with Gs protein
Summary for 7KI0
| Entry DOI | 10.2210/pdb7ki0/pdb |
| EMDB information | 22882 |
| Descriptor | Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (8 entities in total) |
| Functional Keywords | glucagon-like peptide-1 (glp-1) receptor semaglutide cryoem, membrane protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 163832.55 |
| Authors | Zhang, X.,Belousoff, M.J.,Danev, R.,Sexton, P.M.,Wootten, D. (deposition date: 2020-10-22, release date: 2021-08-04, Last modification date: 2025-05-14) |
| Primary citation | Zhang, X.,Belousoff, M.J.,Liang, Y.L.,Danev, R.,Sexton, P.M.,Wootten, D. Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes. Cell Rep, 36:109374-109374, 2021 Cited by PubMed 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. PubMed: 34260945DOI: 10.1016/j.celrep.2021.109374 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.5 Å) |
Structure validation
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