DNA recognition by Cys(2)His(2) zinc finger proteins

Cys(2)His(2) zinc fingers are one of the most common DNA-binding motifs fou nd in eukaryotic transcription factors. These proteins typically contain se veral fingers that make tandem contacts along the DNA. Each finger has a co nserved beta beta alpha structure, and amino acids on the surface of the al pha-helix contact bases in the major groove. This simple, modular structure of zinc finger proteins, and the wide variety of DNA sequences they can re cognize, make them an attractive framework for attempts to design novel DNA -binding proteins. Several studies have selected fingers with new specifici ties, and there clearly are recurring patterns in the observed side chain-b ase interactions. However, the structural details of recognition are intric ate enough that there are no general rules (a "recognition code") that woul d allow the design of an optimal protein for any desired target site. Const ruction of multifinger proteins is also complicated by interactions between neighboring fingers and the effect of the intervening linker. This review analyzes DNA recognition by Cys(2)His(2) zinc fingers and summarizes progre ss in generating proteins with novel specificities from fingers selected by phage display.