DNA Recognition by Cys2His2 Zinc Finger Proteins
Abstract
Cys2His2 zinc fingers are one of the most common DNA-binding motifs found in eukaryotic transcription factors. These proteins typically contain several fingers that make tandem contacts along the DNA. Each finger has a conserved beta beta alpha structure, and amino acids on the surface of the alpha-helix contact bases in the major groove. This simple, modular structure of zinc finger proteins, and the wide variety of DNA sequences they can recognize, make them an attractive framework for attempts to design novel DNA-binding proteins. Several studies have selected fingers with new specificities, and there clearly are recurring patterns in the observed side chain-base interactions. However, the structural details of recognition are intricate enough that there are no general rules (a "recognition code") that would allow the design of an optimal protein for any desired target site. Construction of multifinger proteins is also complicated by interactions between neighboring fingers and the effect of the intervening linker. This review analyzes DNA recognition by Cys2His2 zinc fingers and summarizes progress in generating proteins with novel specificities from fingers selected by phage display.
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The structure of ZFC4 bound to dsDNA resembles that of other C2H2 zinc finger pairs bound to DNA.
“Overall, the structure of ZFC4 bound to dsDNA resembles that of other C2H2 zinc finger pairs bound to DNA (Wolfe et al, 2000) (Fig 1C).”
From Structure of SALL4 zinc finger domain reveals link between AT-rich DNA binding and Okihiro syndrome (2023) · cites this paper as Wolfe et al, 2000
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“Overall, the structure of ZFC4 bound to dsDNA resembles that of other C2H2 zinc fi nger pairs bound to DNA (Wolfe et al, 2000) (Fig 1C).”
Influential
- Authors
- Wolfe, S. A., Nekludova, L., & Pabo, C. O.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Wolfe, Scot A.
- Venue
- Annual Review of Biophysics and Biomolecular Structure
- Publisher
- Annual Reviews
- Published
- 2000-06
- Volume
- 29
- Issue
- 1
- Pages
- 183-212
- ISSN
- 1056-8700 (ISSN-L)
- 1545-4266
- OpenAlex
- W1824346003
- Cited by
- 1,053
- References
- 4
- Citations by year
- 2026: 21 · 2025: 38 · 2024: 59 · 2023: 41 · 2022: 34 · 2021: 46 · 2020: 46 · 2019: 39 · 2018: 57 · 2017: 50 · 2016: 41 · 2015: 45 · 2014: 51 · 2013: 42 · 2012: 37
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biophysics and Biomolecular Structure (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- DNA recognition, DNA-binding motifs, transcription factors, protein-DNA interactions, major groove, phage display, protein design
- MeSH terms
- Amino Acid Sequence, Animals, Cystine, DNA, Histidine, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Transcription Factors, Genetic Therapy, Zinc Fingers, Peptide Library
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