8ID6

Cryo-EM structure of the oleic acid bound GPR120-Gi complex

8ID6 の概要

• エントリーDOI: 10.2210/pdb8id6/pdb
• EMDBエントリー: 35358
• 分子名称: Free fatty acid receptor 4, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total)
• 機能のキーワード: gpcr, gpr120, complex, fatty acid hormones, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 156740.62

構造登録者

Mao, C.,Xiao, P.,Tao, X.,Qin, J.,He, Q.,Zhang, C.,Yu, X.,Zhang, Y.,Sun, J. (登録日: 2023-02-12, 公開日: 2023-03-15, 最終更新日: 2024-10-30)

主引用文献

Mao, C.,Xiao, P.,Tao, X.N.,Qin, J.,He, Q.T.,Zhang, C.,Guo, S.C.,Du, Y.Q.,Chen, L.N.,Shen, D.D.,Yang, Z.S.,Zhang, H.Q.,Huang, S.M.,He, Y.H.,Cheng, J.,Zhong, Y.N.,Shang, P.,Chen, J.,Zhang, D.L.,Wang, Q.L.,Liu, M.X.,Li, G.Y.,Guo, Y.,Xu, H.E.,Wang, C.,Zhang, C.,Feng, S.,Yu, X.,Zhang, Y.,Sun, J.P.
Unsaturated bond recognition leads to biased signal in a fatty acid receptor.
Science, 380:eadd6220-eadd6220, 2023

PubMed Abstract: Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and G or G trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single-nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds. The knowledge gleaned here may facilitate rational drug design targeting to GPR120.

PubMed: 36862765
DOI: 10.1126/science.add6220

実験手法

ELECTRON MICROSCOPY (2.8 Å)