A zinc finger is a protein domain that can bind to DNA. A zinc finger consists of two antiparallel β strands, and an α helix. One very well explored subset of zinc-fingers (the C2H2 class) comprises a pair of cysteine residues in the beta sheets and two histidine residues in the alpha helix which are responsible for binding a zinc ion.
The structure of each individual finger is highly conserved and consists of about 30 amino acid residues, constructed as a ββα fold and held together by the zinc ion. The α-helix occurs at the C-terminal part of the finger, whilst the β-sheet occurs at the N-terminal part.
Many transcription factors (such as Zif268), regulatory proteins, and other proteins that interact with DNA contain zinc fingers. These proteins typically interact with the major groove along the double helix of DNA in which case the zinc fingers are arranged around the DNA strand in such a way that the α-helix of each finger contacts the DNA, forming an almost continuous stretch of α-helices around the DNA molecule.
The binding specificity for 3-4 base pairs are conferred by a short stretch of amino acid residues in the α-helix. The primary position of the amino acid residues within the α-helix interacting with the DNA are at positions -1, 3 and 6 relative to the first amino acid residue of the α-helix. Other amino acid positions can also influence binding specificity by assisting amino acid residues to bind a specific base or by contacting a fourth base in the opposite strand, causing target-site overlap.