Structural basis for the diversity of DNA recognition by bZIP transcription factors

The basic region leucine zipper (bZIP) proteins form one of the largest fam ilies of transcription factors in eukaryotic cells. Despite relatively high homology between the amino acid sequences of the bZIP motifs, these protei ns recognize diverse DNA sequences. Here we report the 2.0 IL resolution cr ystal structure of the bZIP moth of one such transcription factor, PAP1, a fission yeast AP-1-like transcription factor that binds DNA containing the novel consensus sequence TTACGTAA, The structure reveals how the Pap1-speci fic residues of the bZIP basic region recognize the target sequence and sho ws that the side chain of the invariant Asn in the bZIP motif adopts an alt ernative conformation in Pap1, This conformation, which is stabilized by a Pap1-specific residue and its associated water molecule, recognizes a diffe rent base in the target sequence from that in other bZIP subfamilies.