Fig. 3: The molecular mechanism of OEA on stabilizing the HIF-3α-ARNT heterodimer.
From: Identification of oleoylethanolamide as an endogenous ligand for HIF-3α
a Overall crystal structure of the HIF-3α-ARNT in complex with bound OEA. HIF-3α and ARNT are colored in cyan and pink, respectively. b An enlarged view of OEA (magenta) inside its binding pocket, with residues involved in the interaction shown as sticks. c,d Superimposition of HIF-3α-ARNT structures with and without OEA, at the entrance position of HIF-3α PAS-B ___domain (c) and the ARNT A/B loop (d), highlighting the conformational changes after OEA binding. HIF-3α and ARNT proteins in the apo form are colored in orange and green, respectively. e Cα RMSF plots for the ARNT subunit in each system. The highly flexible domains including modelled linkers (black) and A/B loop (magenta) are highlighted. f Cα RMSD plots for the ARNT A/B loop (residues 349-360) in each system. g,h Per-residue decomposition of relative binding energy for residues within the interface between ARNT A/B loop and HIF-3α PAS-B ___domain in HIF-3OEA (g) and HIF-3noOEA (h) systems, respectively. For each system, the 500-ns snapshot is shown. i,j HDX-MS results mapped on the Fα and Gβ regions of HIF-3α. The residues with significantly reduced deuteration levels upon OEA binding are colored in dark blue (−90 to −50%) as compared to the apo form (i) (detailed in Supplementary Fig. 5a), and the R303 in Gβ of HIF-3α forms hydrogen bonds with A/B loop of ARNT (j). Hydrogen bonds are shown in red dotted lines.
