Zinc finger



A zinc finger is a large superfamily of protein domains that can bind to DNA. A zinc finger consists of two antiparallel &beta; sheets, and an &alpha; helix. The zinc ion is crucial for the stability of this domain type - in the absence of the metal ion the domain unfolds as it is too small to have a hydrophobic core.

Classes
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 two other classes of zinc finger proteins are the C4 and C6 classes. Zinc fingers are important in regulation because when interacted with DNA and zinc ion, they provide a unique structural motif for DNA-binding proteins.

Structure
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, while the β-sheet occurs at the N-terminal part.

The consensus sequence of a single finger is: Cys-X2-4-Cys-X3-Phe-X5-Leu-X2-His-X 3 -His

Proteins with Zinc finger
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.

Some primary neuron-specific transcriptional regulator that may be involved in mediating early neural development are also zinc finger-based.

Binding specificity
The binding specificity for 3–4 base pairs is 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.