We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to investigate the influence of OEA on HIF-3A-ARNT.HDX-MS data indicated that OEA binding stabilized multiple residues within the Gβ and Fα regions of HIF-3A PAS-B domain.It is possible that the stabilized Gβ and Fα function as an “interlayer” to further contact with the AB-loop of ARNT.