The single Cys(2)-His(2) zinc finger domain of the GAGA protein flanked by basic residues is sufficient for high-affinity specific DNA binding

Specific DNA binding to the core consensus site GAGAGAG has been shown with an 82-residue peptide (residues 310-391) taken from the Drosophila transcription factor GAGA. Using a series of deletion mutants, it was demonstrated that the minimal domain required for specific binding (residues 310-372) includes a single zinc finger of the Cys(2)-His(2) family and a stretch of basic amino acids located on the N-terminal end of the zinc finger, In gel retardation assays, the specific binding seen with either the peptide or the whole protein Is zinc dependent and corresponds to a dissociation constant of approximate to 5 x 10(-9) M for the purified peptide. It has previously been thought that a single zinc finger of the Cys(2)-His(2) family is incapable of specific, high-affinity binding to DNA. The combination of an N-terminal basic region with a single Cys(2)-His(2) zinc finger in the GAGA protein can thus be viewed as a novel DNA binding domain. This raises the possibility that other proteins carrying only one Cys(2)-His(2) finger are also capable of high-affinity specific binding to DNA.