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Updated: Jun 26, 2025

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Updated understanding of the protein-DNA recognition code used by C2H2 zinc finger proteins
Xing Zhang1, Robert M Blumenthal2, Xiaodong Cheng1
1Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
C2H2 zinc-finger (ZF) proteins form the largest family of DNA-binding transcription factors coded by mammalian genomes. In a typical DNA-binding ZF module, there are twelve residues (numbered from -1 to -12) between the last zinc-coordinating cysteine and the first zinc-coordinating histidine. The established C2H2-ZF "recognition code" suggests that residues at positions -1, -4, and -7 recognize the 5', central, and 3' bases of a DNA base-pair triplet, respectively. Structural studies have highlighted that additional residues at positions -5 and -8 also play roles in specific DNA recognition. The presence of bulky and either charged or polar residues at these five positions determines specificity for given DNA bases: guanine is recognized by arginine, lysine, or histidine; adenine by asparagine or glutamine; thymine or 5-methylcytosine by glutamate; and unmodified cytosine by aspartate. This review discusses recent structural characterizations of C2H2-ZFs that add to our understanding of the principles underlying the C2H2-ZF recognition code.
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