Updated Understanding of the Protein-DNA Recognition Code Used by C2H2 Zinc Finger Proteins

Authors

Xing Zhang
Robert M Blumenthal
Xiaodong Cheng

Publication Date

8-1-2024

Journal

Current Opinion in Structural Biology

DOI

10.1016/j.sbi.2024.102836

PMID

38754172

PMCID

PMC12264921

PubMedCentral® Posted Date

7-16-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

DNA, Humans, Animals, Protein Binding, CYS2-HIS2 Zinc Fingers, Models, Molecular, Zinc Fingers, Binding Sites, DNA-Binding Proteins, C2H2 zinc fingers, transcription factors, protein-DNA interactions, DNA sequence-specific recognition

Published Open-Access

yes

Recommended Citation

Xing Zhang, Robert M Blumenthal, and Xiaodong Cheng, "Updated Understanding of the Protein-DNA Recognition Code Used by C2H2 Zinc Finger Proteins" (2024). Faculty, Staff and Student Publications. 4301.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4301