ENGRAILED AND HOX HOMEODOMAIN PROTEINS CONTAIN A RELATED PBX INTERACTION MOTIF THAT RECOGNIZES A COMMON STRUCTURE PRESENT IN PBX

Hox gene products have the ability to interact with either extradentic le or pbx gene products to bind cooperatively to DNA. The region in Ho x proteins that is required for this interaction is located N-terminal of the homeodomain and contains a highly conserved hexapeptide. We no w show that the engrailed gene products also contain a Pbx interaction motif positioned within a previously conserved region, the EH2 domain . The EH2 domain is located N-terminal of the homeodomain. Two tryptop han residues present in the Drosophila and murine Engrailed EH2 domain are required for cooperativity with extradenticle and Pbx, respective ly. A second conserved domain, EH3, is required as well for cooperativ ity with Pbx, since deletions or an insertion in this region reduce co operative DNA binding. Peptides containing the Pbx interaction motif o f either Engrailed or Hox are capable of destabilizing Engrailed-Pbx a nd Hox-Pbx cooperative DNA binding. These data indicate that the Pbx i nteraction motifs present in Hox and engrailed gene products recognize a common structure present in the Pbx family of homeodomain proteins.