Fig. 2
From: Evasion of immunosurveillance by genomic alterations of PPARγ/RXRα in bladder cancer
S427F mutation in RXRα stabilizes heterodimerization with PPARγ and promotes the agonistic conformation. a Sizing profile of RXRα S427F mutant (green), PPARγ (purple), and the heterodimer (magenta). Both RXRαS427F and PPARγ run as monomers. When mixed together in 1:1 stoichiometry, the elution profile shifts demonstrating formation of the heterodimer in the absence of ligand. b SPR demonstrating enhanced interaction between RXRα S427F mutant and PPARγ. RXRα was immobilized to the CM5 chip by amine coupling and PPARγ was injected in dose response from 3 μM to 24 nM with 60 s association phase and 120 s disassociation. c Overall crystal structure of the heterodimer complex of RXRαS427F mutant (green) and PPARγ (blue) with the co-activator peptide Src1 (red). The agonists 9-cis-retinoic acid and rosiglitazone are rendered as spheres. The AF-2 helix (Helix H12) of PPARγ has been highlighted in magenta. RXRαS427 and PPARγY477 are rendered as sticks and located in the dimer interface. d Zoom in of the heterodimer interface shows the S427F mutation of RXRα (green) introduces a π-stacking interaction with Y477 of PPARg (blue) at the C-terminus (magenta). The 2Fo–Fc electron density map is shown in gray and contoured at 1.2 s
