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Publication Abstract from PubMed

Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many via engagement with more than 40 GPCRs. Searching for receptors to sense beneficial omega-3 FAs of fish oil enabled the identification of GPR120, involving with a spectrum of metabolic diseases. Here, we report six cryo-EM structures of GPR120 in complex with FA hormones or TUG891 and G(i) or G(iq) 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 and may facilitate rational drug design targeting to GPR120.

Unsaturated bond recognition leads to biased signal in a fatty acid receptor.,Mao C, Xiao P, Tao XN, Qin J, He QT, Zhang C, Guo SC, Du YQ, Chen LN, Shen DD, Yang ZS, Zhang HQ, Huang SM, He YH, Cheng J, Zhong YN, Shang P, Chen J, Zhang DL, Wang QL, Liu MX, Li GY, Guo Y, Xu HE, Wang C, Zhang C, Feng S, Yu X, Zhang Y, Sun JP Science. 2023 Mar 2:eadd6220. doi: 10.1126/science.add6220. PMID:36862765^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.