A zinc finger is a finger-shaped protein fold that is formed by specific amino acids in the protein binding to a zinc ion. These proteins often bind to DNA and RNA because their shape allows close interaction of the domain with the nucleotides of DNA and RNA. Their nucleotide binding properties allow them to function in regulating gene expression and in virus assembly.
There are several types of zinc finger structures, but the most common version consists of an alpha helix and a beta sheet, the two most common secondary structures in proteins, on either side of at least one zinc ion. The alpha helix and beta sheet are held in position by cystine and histidine residues, coordinating the zinc ion via their nitrogen and sulfur atoms. The zinc finger binds to DNA, and through the interaction of amino acids at its periphery with base pairs at the center of the DNA double helix. It is a compact protein domain, and its small size allows it to have close proximity with DNA base pairs.
These proteins are the most common transcription factors in living organisms. A transcription factor is a protein that binds to DNA and controls the transfer of genetic information to RNA. The fact that these proteins to target DNA has made them candidates for purposeful re-engineering in order to target DNA sequences of interest.
For example, a Zinc Finger Nuclease (ZFN) is a synthetic protein that has an engineered zinc finger binding domain fused to a restriction endonuclease, or DNA-cleaving enzyme. The ZFN can be used to cut DNA at specific locations, and is a useful tool to promote site-specific recombination of DNA. Engineered zinc fingers can also be used as artificial transcription factors.
Zinc finger domains are found in some viral proteins, including the neocapsid (NC) protein of the Human Immunodeficiency-1 (HIV-1) virus. NC is an attractive antiviral target because it is important for viral assembly and is highly conserved. Inhibitors that specifically target the zinc fingers of viral and retroviral proteins could be used to prevent virus replication. Obtaining antiviral compounds of this nature is an active area of biomedical research.
These proteins play important roles in the normal metabolism of cells. To be effective, anti-retroviral compounds must specifically target retroviral zinc finger proteins. These retroviral proteins have distinct amino acid sequences and structural differences from cellular zinc finger proteins, so obtaining selective inhibitors is an achievable goal.
