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Stevens K , Cirillo L , Zaret KS
Creating temperature-sensitive winged helix transcription factors. Amino acids that stabilize the DNA binding domain of HNF3
J Biol Chem. 2000 Sep 29;275(39) :30471-7
PMID: 10896667 URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10896667
AbstractWinged helix transcription factors contain two polypeptide loops, or "wings," that make minor groove contacts with DNA from either side of a three-helix bundle that binds the DNA major groove. While wing 1 is stabilized by a beta-sheet, parameters that stabilize wing 2 are unknown. Herein we identify two bulky aromatic residues in wing 2 that stabilize the loop structure and, thereby, the entire protein's DNA binding and transcriptional stimulatory activity by interacting with other residues in the three-helix bundle. Mutations of these wing 2 residues create proteins that are temperature-sensitive for transcriptional activity. Aromatic and/or hydrophobic residues are highly conserved among the 150 known winged helix proteins, suggesting conserved function. We suggest that the winged helix structure evolved by the acquisition of aromatic and/or hydrophobic residues in distal polypeptide sequences that helped stabilize the association of a protein loop (wing 2) with the three-helix bundle, thereby enhancing DNA binding.
Notes20459120 0021-9258 Journal Article