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-binding region. These proteins recognize extended DNA sequence elements flanking the core recognition element bound by canonical bZIP proteins. We have investigated the causes for the differences in DNA recognition between Maf and other bZIP family proteins through studies of Maf secondary structure, trypsin sensitivity, binding affinity, dissociation rate and DNA contacts. Our results show that specific DNA binding by Maf is coupled to a conformational 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 the conformational change required for Maf recognition of the extended elements. Nucleotide base contacts made by Maf differ from those made by canonical bZIP proteins. Taken together, our results suggest that the unusual DNA binding specificity of Maf family proteins is mediated by concerted folding of structurally unrelated DNA recognition motifs.
Dlakić
M
M
Howard Hughes Medical Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0650, USA.
Grinberg
A V
AV
Leonard
D A
DA
Kerppola
T K
TK
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D051790:G-Box Binding Factors; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D001426:Bacterial Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; C081169:Maf protein, Bacillus subtilis; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D004247:DNA