Homeodomain Fold

The homeodomain fold is a protein structural domain that binds DNA or RNA and is thus commonly found in transcription factors. The fold consists of a 60-amino acid helix-turn-helix structure in which three alpha helices are connected by short loop regions. The N-terminal two helices are antiparallel and the longer C-terminal helix is roughly perpendicular to the axes established by the first two. It is this third helix that interacts directly with DNA. Homeodomain folds are found exclusively in eukaryotes but have high homology to lambda phage proteins that alter the expression of genes in prokaryotes. Many homeodomains induce cellular differentiation by initiating the cascades of coregulated genes required to produce individual tissues and organs, while homeodomain proteins like NANOG are involved in maintaining pluripotency.