<p>Winged helix DNA-binding proteins share a related winged helix-turn-helix DNA-binding motif, where the "wings", or loops, are small beta-sheets. The winged helix motif consists of two wings (W1, W2), three alpha helices (H1, H2, H3) and three beta-sheets (S1, S2, S3) arranged in the order H1-S1-H2-H3-S2-W1-S3-W2 [<cite idref="PUB00013195"/>]. The DNA-recognition helix makes sequence-specific DNA contacts with the major groove of DNA, while the wings make different DNA contacts, often with the minor groove or the backbone of DNA. Several winged-helix proteins display an exposed patch of hydrophobic residues thought to mediate protein-protein interactions.</p><p>Many different proteins with diverse biological functions contain a winged helix DNA-binding domain, including transcriptional repressors such as biotin repressor, LexA repressor and the arginine repressor [<cite idref="PUB00004803"/>]; transcription factors such as the hepatocyte nuclear factor-3 proteins involved in cell differentiation, heat-shock transcription factor, and the general transcription factors TFIIE and TFIIF [<cite idref="PUB00013196"/>, <cite idref="PUB00013197"/>]; helicases such as RuvB that promotes branch migration at the Holliday junction, and CDC6 in the pre-replication complex [<cite idref="PUB00013198"/>, <cite idref="PUB00013199"/>]; endonucleases such as FokI and TnsA [<cite idref="PUB00007438"/>]; histones; and Mu transposase, where the flexible wing of the enhancer-binding domain is essential for efficient transposition [<cite idref="PUB00013200"/>].</p>