Ordered structure-forming properties of the intrinsically disordered AB region of hRXRγ and its ability to promote liquid-liquid phase separation

•We describe the biochemical and biophysical properties of AB_hRXG.•AB_hRXG shows the structural and functional characteristics of PMG-like group of IDPs.•AB_hRXG exhibits an ability to promote the formation of LLPS. The retinoid X receptor (RXR) is a member of the nuclear receptor (NR) superfamily that occupies the central position among other NRs by forming both homodimers and heterodimers with other representatives of the family. RXR shares similar structural domains with other members of NRs. The major differences in the subtypes and isoforms of RXR are in the AB region. To date, there have been no data concerning the molecular properties of the AB region of hRXRγ (AB_hRXG). Here, we describe the biochemical and biophysical properties of the recombinant AB_hRXG. The results indicate that AB_hRXG shows the structural and functional characteristics of the pre-molten globule-like (PMG-like) group of intrinsically disordered proteins (IDPs) and also has a significant propensity for folding. We also present the first experimental evidence showing that the AB region of NRs promotes the formation of liquid–liquid phase separation (LLPS).