8ID8

Cryo-EM structure of the TUG891 bound GPR120-Gi complex

Summary for 8ID8

• Entry DOI: 10.2210/pdb8id8/pdb
• EMDB information: 35359
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Free fatty acid receptor 4, ... (6 entities in total)
• Functional Keywords: gpcr, gpr120, complex, fatty acid hormones, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 156822.57

Authors

Mao, C.,Xiao, P.,Tao, X.,Qin, J.,He, Q.,Zhang, C.,Yu, X.,Zhang, Y.,Sun, J. (deposition date: 2023-02-12, release date: 2023-03-15, Last modification date: 2023-05-03)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3 Å)