Functional characterization of DNA-binding domains of the subunits of the heterodimeric aryl hydrocarbon receptor complex imputing novel and canonical basic helix-loop-helix protein-DNA interactions. 
The aryl hydrocarbon receptor (AHR) and the aryl hydrocarbon receptor nuclear translocator (ARNT) belong to a novel subclass of basic helix-loop-helix transcription factors.  The AHR.ARNT heterodimer binds to the xenobiotic responsive element (XRE).  Substitution of each of four amino acids in the basic region of ARNT with alanine severely diminishes or abolishes XRE binding, intimating that these amino acids contact DNA bases.  Three of these amino acids are conserved among basic helix-loop-helix proteins, and the corresponding amino acids of Max and USF are known to contact DNA bases.  Alanine scanning mutagenesis of the basic domain of AHR and substitution with conservative amino acids at particular positions in this domain and in a more amino-proximal AHR segment previously shown to be required for XRE binding (Fukunaga, B. N., and Hankinson, O. (1996) J. Biol.  Chem.  271, 3743-3749) demonstrate that the most carboxyl-proximal amino acid position of the basic domain and a position within the amino-proximal segment are intolerant to amino acid substitution with regard to XRE binding, suggesting that these two amino acids make base contacts.  Amino acid positions in these AHR regions and in the ARNT basic region less adversely affected by substitution are also identified.  The amino acids at these positions may contact the phosphodiester backbone.  The apparent bipartite nature of the DNA binding region of AHR and the identity of those of its amino acids that apparently make DNA contacts impute a novel protein-DNA binding behavior for AHR.