ZincFinger

A zinc finger is a small protein structural motif stabilized by one or more zinc ions that enables specific interactions with nucleic acids or other proteins. The best-characterized class is the C2H2 zinc finger, in which a finger consists of about 23–30 amino acids forming a beta-hairpin followed by an alpha-helix, with a Zn2+ ion coordinated by two cysteines and two histidines in a Cys2His2 motif. Other zinc-binding types include C3H1, CCCH, and C4-type zinc ribbons, each defined by distinct patterns of cysteine and histidine ligands and corresponding folds.

Function and distribution: Zinc fingers frequently occur in tandem repeats within transcription factors, enabling the recognition of extended DNA sequences. The recognition helix of each finger makes sequence-specific contacts with base pairs in the major groove of DNA. Beyond DNA binding, some zinc finger motifs bind RNA or mediate protein–protein interactions. Zinc finger proteins participate in diverse cellular processes, including development, differentiation, and gene regulation, and are especially abundant in eukaryotes.

History and technology: Zinc fingers were first described in the 1980s, with landmark work by Aaron Klug and colleagues on transcription factor TFIIIA from Xenopus laevis, which revealed the zinc-coordinating motif and its folding. The modular nature of zinc fingers led to engineered proteins, such as zinc finger nucleases (ZFNs), where finger arrays are fused to nucleases to create targeted genome-editing tools. While newer technologies like TALENs and CRISPR/Cas systems have become dominant for genome engineering, zinc finger domains remain important in native proteins and continue to inform protein design and synthetic biology.