Working together to bind DNA. The specificity of DNA binding by the ets protein GABPa is determined by formation of a heterotetramer (a2-b2) that recognizes a binding site with two 5¢-GGA-3¢ cores. In the a subunit, the ETS domain functions in DNA binding, inhibitory sequences are proposed to negatively regulate DNA binding, and the pointed (PNT) domain is a structural domain conserved in some ETS domain proteins. In the b subunit, the leucine zipper motif (LEU ZIPPER) mediates b-subunit interaction, the transactivation domain is required for transcriptional activation, and ankyrin repeats form the interface with the a subunit. Flexibility in the linkage between the leucine zipper region and ankyrin repeats of GABPb is proposed to accommodate recognition of direct repeats of GGA (shown) or inverted repeats of the GGA core with variable spacing. The asterisks indicate phosphate contacts detected in the crystal structure.
