Structure comparison of two conserved HNF-3/fkh proteins HFH-1 and genesis indicates the existence of folding differences in their complexes with a DNA binding sequence.

The hepatocyte nuclear factor 3 (HNF-3)/fork head (fkh) family contains a large number of transcription factors that recognize divergent DNA sequences via a winged helix binding motif. HNF-3/fkh proteins show a broad profile of DNA sequence-specificity in which one DNA sequence can be recognized by more than one HNF-3/fkh protein and each individual HNF-3/fkh protein has several DNA binding sequences. In this study, heteronuclear NMR methods were used to study the structures of the DNA binding domain of a conserved winged helix protein HFH-1 and its DNA complexes. The structural comparison of winged helix proteins HFH-1 and Genesis and their DNA complexes indicates that even two highly conserved HNF-3 family members can adopt different local structures when they contact an identical DNA binding sequence, while one of these two HNF-3 proteins seems to adopt only slightly different structures on different DNA binding sites.