Zinc Fingers: Structure and Design

Abstract Zinc fingers are small, compact protein subunits, folding around chelated zinc ions. Functionally, these motifs carry out a wide variety of tasks within cells by providing stable structural scaffolds and driving critical binding interactions, especially among proteins, DNA, and RNA. The motifs are particularly important in gene regulation, where many proteins employ them to bind DNA in a sequence-specific manner, to activate or inhibit particular genes. Zinc fingers are extremely versatile, as can be seen by their abundance in nature: over 700 proteins contain Cys2–His2 zinc fingers in the human genome alone and they are thought to be the largest protein superfamily in metazoans. Importantly, chains of artificial zinc fingers may be designed to bind novel DNA sequences following a code. Simple worked examples of how to do this are explained here. Engineered zinc fingers have numerous applications in both biotechnology and medicine.