The fork head protein of Drosophila melanogaster, a transcription factor that promotes terminal rather than segmental development, contains neither homeodomains nor zinc-fingers characteristic of other transcription factors.[3] Instead, it contains a distinct type of DNA-binding region, containing around 100 amino acids, which has since been identified in a number of transcription factors (including D. melanogaster FD1-5, mammalian HNF3, human HTLF, Saccharomyces cerevisiae HCM1, etc.). This is referred to as the fork head domain but is also known as a "winged helix".[3][4][5] The fork head domain binds B-DNA as a monomer,[4] but shows no similarity to previously identified DNA-binding motifs. Although the domain is found in several different transcription factors, a common function is their involvement in early developmental decisions of cell fates during embryogenesis.[5] Members of the class O of forkhead box transcription factors (FoxO) have important roles in metabolism, cellular proliferation, stress tolerance and probably lifespan.[6]
^Marsden I, Jin C, Liao X (May 1998). "Structural changes in the region directly adjacent to the DNA-binding helix highlight a possible mechanism to explain the observed changes in the sequence-specific binding of winged helix proteins". J. Mol. Biol. 278 (2): 293–9. doi:10.1006/jmbi.1998.1703. PMID9571051.
^ abClark KL, Halay ED, Lai E, Burley SK (July 1993). "Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5". Nature. 364 (6436): 412–20. doi:10.1038/364412a0. PMID8332212. S2CID4363526.
^van der Horst A, Burgering BM (June 2007). "Stressing the role of FoxO proteins in lifespan and disease". Nature Reviews Molecular Cell Biology. 8 (6): 440–50. doi:10.1038/nrm2190. PMID17522590. S2CID31546098.