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Cartoon representation of the zinc finger motif of proteins, consisting of an α helix and an antiparallel β sheet. The zinc ion (green) is coordinated by two histidine residues and two cysteine residues.

Cartoon representation of the protein Zif268 (blue) containing three zinc fingers in complex with DNA (orange). The coordinating amino acid residues of the middle zinc ion (green) are highlighted.

A zinc finger is a large superfamily of protein domains that can bind to DNA. A zinc finger consists of two antiparallel β sheets, and an α 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.

One very well explored sub-set 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.

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-X_2-4-Cys-X₃-Phe-X₅-Leu-X₂-His-X3-His

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.

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.

• Zinc finger inhibitor
• Steroid hormone receptor

Luscombe, Nicholas, et al (9 June 2000). "An overview of the structures of protein-DNA complexes". Genome Biology Review 1 (1): 4-5. 

• Zinc Finger Tools design and information site
• Entry for zinc finger class C2H2 in the SMART database
• The Zinc Finger Consortium