Family

Many different protein families are capable of binding DNA through a variety of protein domains with different tertiary structures. The helix-turn-helix (HTH) class of DNA binding proteins is one of the best understood and most diverse. This class of proteins contains a conserved motif consisting of two alpha helices oriented perpndicular to one another and seperated by a short linker sequence. The second helix (recognition helix) encodes the DNA binding capacity of HTH proteins by making direct contacts with the DNA double helix. Most HTH proteins associate preferentially with a specific nucleotide sequence because the amino acids within the recognition helix make specific chemical bonds with side chains on individual nucleotide bases.

In addition to binding DNA individually, HTH proteins are capable of interacting with themselves to form dimers which can bind DNA cooperatively. In this dimeric form the two DNA binding domains (one on each protein) are separated by 3.4 nM, the exact length of one turn of the DNA double helix. Upon binding DNA, helix-turn-helix proteins affect the level of transcription of genes within the vicinity of the binding site. HTH proteins have been shown to both up and down regulate transcription but it is unclear how these proteins interact with the transcriptional machinery and effect this change.