DNA sequence-dependent folding determines the divergence in binding specificities between Maf and other bZIP proteins

Maf family transcription factors are atypical basic region-leucine zipper ( bZIP) proteins that contain a variant basic region and an ancillary DNA-bin ding region, These proteins recognize extended DNA sequence elements flanki ng the core recognition element bound by canonical bZIP proteins. We have i nvestigated the causes for the differences in DNA recognition between Maf a nd other bZIP family proteins through studies of Maf secondary structure, t rypsin sensitivity, binding affinity, dissociation rate and DNA contacts. O ur results show that specific DNA binding by Maf is coupled to a conformati onal change involving both the basic and ancillary DNA-binding regions that depends on the extended DNA sequence elements. Two basic region amino acid residues that differ between Maf and canonical bZIP proteins facilitate th e conformational change required for Maf recognition of the extended elemen ts, Nucleotide base contacts made by Maf differ from those made by canonica l bZIP proteins. Taken together, our results suggest that the unusual DNA b inding specificity of Maf family proteins is mediated by concerted folding of structurally unrelated DNA recognition motifs.