Each monomer incorporates two α helices, joined by a short strand of amino acids, that bind to the major groove of DNA.
[1] The discovery of the helix-turn-helix motif was based on similarities between several genes encoding transcription regulatory proteins from bacteriophage lambda and Escherichia coli: Cro, CAP, and λ repressor, which were found to share a common 20–25 amino acid sequence that facilitates DNA recognition.
The recognition and binding to DNA by helix-turn-helix proteins is done by the two α helices, one occupying the N-terminal end of the motif, the other at the C-terminus.
It binds to the major groove of DNA through a series of hydrogen bonds and various Van der Waals interactions with exposed bases.
A fragment of Engrailed homeodomain encompassing only the two helices and the turn was found to be an ultrafast independently folding protein domain.