Here is an image of a protein, the transcription factor (TF) AP-1, bound to double stranded (ds) Deoxyribonucleic acid (DNA) obtained from x-ray crystallography data. Notice how the alpha-helices (purple spirals) fit in between two adjacent major grooves of the DNA (yellow and red alpha-helix). Interestingly, the TF binds a sequence specific site: TTANTAA with T = Thymine, A = Adenine, and N = any nucleotide ATG or C (G = Guanine, C = Cytosine) without having any complementary nucleotide bases contained within the protein's sequence, since proteins are made of amino acids and not nucleic acids. One major driving force behind the binding specificity is hydrogen bonding (non-covalent bonds between F-H, O-H, or N-H that have about 4.5 kcal/mole bond disassociation energy -- for comparison, a covalent Oxygen-Hydrogen bond has 110 kcal/mole bond disassociation energy). H-bonds must be at a prescribed distance of 2.8-3.0Å to form. If this protein, AP-1 wants to bind DNA at a specific sequence, it must have amino acids with Nitrogens and/or Oxygens strategically located within the purple helices in such a manner that they are close enough to hydrogens bound to Oxygen and/or Nitrogen on the nucleotide bases of DNA within that sequence of TTANTAA. Additionally, covalent O-H and N-H substituant groups located on amino acid residues can H-bond to Oxygens and Nitrogens available on the DNA bases as long as they are situated so that when AP-1's alpha-helices enter the adjacent major grooves, these hydrogens are located within 2.8-3Å of a free oxygen or nitrogen.

Common to many DNA-binding proteins is a Helix-turn-Helix, meaning there are two alpha-helices bound by a short strand of amino acids. In the case of AP-1 there is a tertiary structure of anti-parallel beta-sheets connecting the alpha-helices as indicated by the purple arrows. The head of the arrow indicates the C-terminus while the tail of the arrow indicates the N-terminus of a polypeptide going from N-C-C-N-C-C-N-C-C. This may suggest a functional role for the beta-sheets in that conformational changes of these sheets can alter DNA-binding and ultimately gene expression.

-Eric