Selected peptide extension contacts hydrophobic patch on neighboring zinc finger and mediates dimerization on DNA

Protein-protein interactions often play a crucial role in stabilizing prote in-DNA complexes and thus facilitate site-specific DNA recognition. We have worked to incorporate such protein-protein contacts into our design and se lection strategies for short peptide extensions that promote cooperative bi nding of zinc finger proteins to DNA. We have determined the crystal struct ure of one of these fusion protein-DNA complexes. The selected peptide exte nsion was found to mediate dimerization by reaching across the dyed axis an d contacting a hydrophobic patch on the surface of the zinc finger bound to the adjacent DNA site. The peptide-zinc finger protein interactions observ ed in this structure are similar to those of some homeodomain heterodimers. We also find that the region of the zinc finger surface contacted by the s elected peptide extension corresponds to surfaces that also make key intera ctions in the zinc finger proteins GLI and SW15.