Fig. 3: Structures of GPR120 bound to ALA and EDA.
a,b, Binding of ALA (a) and EDA (b) within the ligand binding pocket. The enlarged view highlights the interactions involving the unsaturated bonds with GPR120. c–e, ALA activates GPR120. Structures of ALA bound to GPR120, with the core (c), the extracellular (d), and the intracellular views (e), generated by Alpha-fold, as shown in rainbow color. Residues participating in the interactions with ALA C-terminal are labeled in c. The gray dashed line illustrates the notable changes in TM6 between the ALA-activated GPR120 and the Alpha-fold-predicted inactive form in e. f, The binding pocket residues of GPR120 interacting with ALA. Throughout the 50 ns simulation, residues V307, G122, and S123 exhibit stable interactions with ALA, while other residues show variable interactions. g, Dot plot visualization of the binding-pocket residues of GPR120 involved in interactions with the ligand ALA. Green dots denote stable interactions consistent with the cryo-EM structure of linoleic acid bound to GPR120 (PDB 8ID6), while orange dots indicate stable interactions observed in our simulation. Gray dots represent dynamic interactions. h–j, Saturation binding curves of FITC–ALA (h) or FITC–EDA (i) or FITC–ALA in the presence of 10 μM EDA (j) toward GPR120. Data are presented as mean ± s.e.m. from three independent experiments performed in triplicates (n = 9).
