Fig. 2: Integrative modelling of the FXR-RXRα heterodimer binding to hSHP-1.

A Multi-domain model of FXR₁₂₀-RXRα₉₈-hSHP-1 (FXR, pink; RXRα, slate). Luciferase reporter gene assay was used to detect the effect of FXR and RXRα mutations in B the FXR-DBD and RXRα-DBD interface, C the putative DNA binding interface of the FXR-DBD and RXRα-DBD and D the FXR-LBD and FXR-DBD interface on the transcriptional activity of FXR₁₂₀-RXRα₉₈ on hSHP-1 in the presence of GW4064(100 nM) and 9cRA (100 nM). Data represents mean from n = 3 experiments, Error bars represent SEM, ns represent no significance (P > 0.05). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by one-way ANOVA. E The mutated residues mapped to the FXR-RXRα-hSHP-1 model. The amino acids mutated at the interface between FXR-DBD and RXRα-DBD are highlighted in orange. The limon color represents the mutant residues at the DNA-binding interface of FXR-RXRα-DBD. The magenta color indicates the mutated residues located at the interface between FXR-LBD and FXR-DBD.