Abstract: The yeast Saccharomyces cerevisiae has three cell types distinguished by the proteins encoded in their mating-type (MAT) loci: the a and α haploids, which express the DNA-binding proteins a1, and α1 and α2, respectively, and the a/α diploid which expresses both a1 and α2 proteins. In a/α cells, a1−α2 heterodimers repress haploid-specific genes and MATα1, whereas α2 homodimers repress a-specific genes, indicating dual regulatory functions for α2 in mating-type control. We previously demonstrated that the two leucine zipper-like coiled-coil motifs, called α2A and α2B, in the α2 N-terminal domain are important to a1−α2 heterodimerization. A unique feature of α2B is the occurrence of three atypical amino acid residues at a positions within the hydrophobic core. We have conducted mutational analyses of α2B peptides and the full-length protein. Our data suggest that these residues may play a critical role in partitioning of the α2 protein between heterodimerization with a1 and homodimerization with itself.