HDX Reveals DNA Binding Modulates Ligand-dependent Co-activator Interaction with the VDR/RXR Nuclear Receptor Complex

摘要

Either of the ligands can induce the cross-communications between two LBDs, which is overridden when the other ligand is present. Either of the ligands can induce the conformational change in VDR DBD and that is independent of the presence of the other ligand. DNA binding directly influences the AF2 conformation for both receptors and this influence is ligand-dependent, so specific DNA sites may influence coactivator interaction with the complex. VDR hinge region showed very different conformational dynamics induced by VDREdr3 and Cyp24vdre, strongly suggesting that VDR hinge is involved in DNA recognition. The stoichiometry of SRC1 recruitment to RXR-VDR heterodimer complex is a single SRC1 molecule per heterodimer and RXR-VDR heteroidmer behaves as a conditionally permissive heterodimer. DNA binding also regulates SRC1 recruitment, so DNA functions as an allosteric ligand.