9XFJ
Cryo-EM structure of the Bavachalcone bound GPR120-Giq complex (local refinement)
This is a non-PDB format compatible entry.
Summary for 9XFJ
| Entry DOI | 10.2210/pdb9xfj/pdb |
| EMDB information | 66824 |
| Descriptor | Free fatty acid receptor 4, Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(q) subunit alpha, (~{E})-3-(4-hydroxyphenyl)-1-[5-(3-methylbut-2-enyl)-2,4-bis(oxidanyl)phenyl]prop-2-en-1-one (3 entities in total) |
| Functional Keywords | ffar4, agonist, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 81412.78 |
| Authors | |
| Primary citation | Kong, Y.,Wang, J.,Wang, Z.,Yang, S.,Ye, X.,Wang, W.,Wang, H.,Deng, W.,Liu, Y.,Xu, F.,Hou, T.,Zhao, Y.,Zhang, B.,Yu, X.,Chen, Y.,Liang, X.,Zhu, S. G alpha q activation of free fatty acid receptor 4 suppresses metabolic dysfunction by disrupting Nr1h3-PPAR gamma axis. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Maintenance of glucose and lipid homeostasis is essential for metabolic health, and its dysregulation, driven by complex gene-environment interactions-underlies various metabolic disorders. Free fatty acid receptor 4 (FFAR4) has been proposed to link dietary signals with genetic metabolic predisposition, yet the precise mechanisms underlying the pathophysiological function of FFAR4 remain elusive and lack of the highly selective FFAR4 agonists. Our study shed light on the pivotal role of FFAR4 in metabolic homeostasis within metabolic organs. Hepatic FFAR4 deficiency in mice exacerbates lipid accumulation and promoted severe steatosis, whereas its overexpression ameliorates diet-induced metabolic dysfunction. Mechanistically, suppression of hepatic FFAR4 promotes lipogenesis by enhancing co-activation of the nuclear receptor Nr1h3 and PPARγ. Furthermore, we identify bavachalcone, a non-carboxylated compound isolated from the traditional Chinese medicine Psoralea corylifolia L., as a functionally effective FFAR4 agonist, which could robustly attenuate metabolic dysfunction. Structural analysis using cryo-electron microscopy reveals the binding mode of bavachalcone within the FFAR4-Gα complex and illuminated the underlying mechanisms. In conclusion, our findings highlight an indispensable role of hepatic FFAR4 in counteracting metabolic dysregulation and identify bavachalcone as a selective and translatable FFAR4 agonist worthy of further clinical evaluation. PubMed: 42457710DOI: 10.1038/s41467-026-75589-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.25 Å) |
Structure validation
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