7KI0

Semaglutide-bound Glucagon-Like Peptide-1 (GLP-1) Receptor in Complex with Gs protein

7KI0 の概要

• エントリーDOI: 10.2210/pdb7ki0/pdb
• EMDBエントリー: 22882
• 分子名称: 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)
• 機能のキーワード: glucagon-like peptide-1 (glp-1) receptor semaglutide cryoem, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 163832.55

構造登録者

Zhang, X.,Belousoff, M.J.,Danev, R.,Sexton, P.M.,Wootten, D. (登録日: 2020-10-22, 公開日: 2021-08-04, 最終更新日: 2025-05-14)

主引用文献

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

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: 34260945
DOI: 10.1016/j.celrep.2021.109374

実験手法

ELECTRON MICROSCOPY (2.5 Å)