Dimerization among nuclear hormone receptors

Abstract

The nuclear hormone receptors comprise a superfamily of ligand-modulated transcription factors that regulate homeostasis, reproduction, development, and differentiation. The DNA-binding domain of the nuclear hormone receptors contains two zinc finger motifs and binds to response elements composed of two-half-sites separated by a variably sized gap. DNA binding specificity is accomplished by a combination of mechanisms. First, discrimination among half-site sequences is mediated by three amino acids within the first zinc finger. Second, response elements with different half-site spacing can be discriminated by five amino acids in the second zinc finger, which may act as a dimerization interface. A second dimerization signal is embedded within the ligand-binding domain of several receptors. Ligand binds to sequences adjacent to this region and enhances dimerization. It is possible that dimerization of these receptors could account for certain physiologic and pathologic conditions observed in vivo.