InterPro domain: IPR036388

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 [ 1 ]. 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.

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 [ 2 ]; 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 [ 3 , 4 ]; helicases such as RuvB that promotes branch migration at the Holliday junction, and CDC6 in the pre-replication complex [ 5 , 6 ]; endonucleases such as FokI and TnsA [ 7 ]; histones; and Mu transposase, where the flexible wing of the enhancer-binding domain is essential for efficient transposition [ 8 ].

1. Winged helix proteins. Curr. Opin. Struct. Biol. 10, 110-6
2. Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. Proc. Natl. Acad. Sci. U.S.A. 89, 9257-61
3. Hepatocyte nuclear factor 3/fork head or "winged helix" proteins: a family of transcription factors of diverse biologic function. Proc. Natl. Acad. Sci. U.S.A. 90, 10421-3
4. The wing in yeast heat shock transcription factor (HSF) DNA-binding domain is required for full activity. Nucleic Acids Res. 29, 1715-23
5. Crystal structure of the RuvA-RuvB complex: a structural basis for the Holliday junction migrating motor machinery. Mol. Cell 10, 671-81
6. Structure and function of Cdc6/Cdc18: implications for origin recognition and checkpoint control. Mol. Cell 6, 637-48
7. Structure of the multimodular endonuclease FokI bound to DNA. Nature 388, 97-100
8. The wing of the enhancer-binding domain of Mu phage transposase is flexible and is essential for efficient transposition. Proc. Natl. Acad. Sci. U.S.A. 93, 1146-50