Dimerization interfaces of thyroid hormone, retinoic acid, vitamin D, and retinoid X receptors.

A subclass of erbA-related nuclear receptors has been shown to require interaction with an auxiliary protein(s) from nuclear extract in order to achieve high affinity DNA binding in vitro. The retinoid X receptor recently has been demonstrated to be such an auxiliary protein as it enhances specific DNA binding by thyroid hormone receptors, retinoic acid receptors, and the vitamin D receptor. Mutation of a highly conserved 20-amino acid region within the ligand-binding domain of thyroid hormone receptor beta disrupts its physical association with auxiliary protein from JEG-3 cells as well as with recombinant retinoid X receptor beta. The homologous 20-amino acid regions from retinoic acid receptor alpha and the vitamin D receptor also are critical determinants of the heterodimeric interaction between these receptors and JEG-3 cell auxiliary protein as well as retinoid X receptor beta. However, the same region of retinoid X receptor beta appears to play a minor, if any, role in heterodimerization. In addition, transfection studies indicate that disruption of heterodimerization impairs the ability of these receptors to function as ligand-dependent transcriptional activators.