The structure of a complex containing the homeodomain repressor protein MAT alpha 2 and the MADS-box transcription factor MCM1 bound to DNA has been determined by X-ray crystallography at 2.25 Angstrom resolution. It reveals the protein-protein interactions responsible for cooperative binding of MAT alpha 2 and MCM1 to DNA. The otherwise flexible amino-terminal extension of the MAT alpha 2 homeodomain forms a beta-hairpin that grips the MCM1 surface through parallel beta-strand hydrogen bonds and dose-packed, predominantly hydrophobic, side chains. DNA bending induced by MCM1 brings the two proteins closer together, facilitating their interaction. An unusual feature of the complex is that an eight-amino-acid sequence adopts an alpha-helical conformation in one of two copies of the MAT alpha 2 monomer and a beta-strand conformation in the other. This ＇chameleon＇ sequence of MAT alpha 2 may be important for recognizing natural operator sites.