Polyglutamine tracts are found in different proteins including transcription factors and cofactors as well as in triplet repeat disease gene products. To characterize the protein motif that binds to the polyglutamine tract, we screened a human embryonic brain cDNA library with the polyglutamine tract of Brn-2 as bait using the yeast two-hybrid method. All six isolated clones encoding polyglutamine tract binding proteins were rich in polar amino acids. Three of these clones could form polar helical structures. These observations suggest that polar amino acid-rich sequences are essential for binding to the polyglutamine tract.