THE YEAST ALPHA-2 AND MCM1 PROTEINS INTERACT THROUGH A REGION SIMILARTO A MOTIF FOUND IN HOMEODOMAIN PROTEINS OF HIGHER EUKARYOTES

Homeodomain proteins are transcriptional regulatory factors that, in g eneral, bind DNA with relatively low sequence specificity and affinity , One mechanism homeodomain proteins use to increase their biological specificity is through interactions with other DNA-binding proteins. W e have examined how the yeast (Saccharomyces cerevisiae) homeodomain p rotein alpha 2 specifically interacts with Mcm1, a MADS box protein, t o bind DNA specifically and repress transcription, A patch of predomin antly hydrophobic residues within a region preceding the homeodomain o f alpha 2 has been identified that specifies direct interaction with M cm1 in the absence of DNA, This hydrophobic patch is required for coop erative DNA binding with Mcm1 in vitro and for transcriptional repress ion in vivo, We have also found that a conserved motif, termed YPWM, f requently found in homeodomain proteins of insects and mammals, partia lly functions in place of the patch in alpha 2 to interact with Mcm1, These findings suggest that homeodomain proteins from diverse organism s mag use analogous interaction motifs to associate with other protein s to achieve high levels of DNA binding affinity and specificity.