Protein-Protein Interaction Domains and the Heterodimerization of Thyroid Hormone Receptor Variant α2 with Retinoid X Receptors

Heterodimerization between thyroid hormone receptors (TRs) and retinoid X receptors (RXRs) is mediated by a weak dimerization interface within the DNA- binding domains (DBDs) and a strong interface within the C-terminal ligand- binding domains of the receptors. Previous studies have shown that the conserved ninth heptad in the TR ligand-binding domain appears to play a critical role in heterodimerization with RXR. However, despite lacking the full ninth heptad, TR variant α2 (TRvα2) can heterodimerize with RXR on specific direct repeat response elements, but not on palindromic elements or in solution. Two possibilities may account for TRvα2-RXR heterodimerization on direct repeats. First, the DBD of TRvα2 may play a critical role in heterodimerization with RXR. Second, a specific sequence within the unique C terminus of TRvα2 may promote the formation of TRvα2-RXR heterodimers. In this study, we used receptor chimeras in which the DBD of RXR was replaced by either the TR DBD or an unrelated DBD from the m...