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 orde r to achieve high affinity DNA binding in vitro. The retinoid X recept or recently has been demonstrated to be such an auxiliary protein as i t enhances specific DNA binding by thyroid hormone receptors, retinoic acid receptors, and the vitamin D receptor. Mutation of a highly cons erved 20-amino acid region within the ligand-binding domain of thyroid hormone receptor beta disrupts its physical association with auxiliar y protein from JEG-3 cells as well as with recombinant retinoid X rece ptor beta. The homologous 20-amino acid regions from retinoic acid rec eptor alpha and the vitamin D receptor also are critical determinants of the heterodimeric interaction between these receptors and JEG-3 cel l auxiliary protein as well as retinoid X receptor beta. However, the same region of retinoid X receptor beta appears to play a minor, if an y, role in heterodimerization. In addition, transfection studies indic ate that disruption of heterodimerization impairs the ability of these receptors to function as ligand-dependent transcriptional activators.