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DNA recognition by Cys2His2 zinc finger proteins
S A Wolfe1, L Nekludova, C O Pabo
1Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Annual Review of Biophysics and Biomolecular Structure
|August 15, 2000
Summary
Cys2His2 zinc fingers are key DNA-binding proteins in eukaryotes. While designing new proteins with specific DNA recognition is challenging due to complex interactions, progress is being made using phage display techniques.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- Cys2His2 zinc fingers are prevalent DNA-binding motifs in eukaryotic transcription factors.
- These proteins utilize a conserved beta-beta-alpha structure for DNA interaction, primarily through alpha-helix surface amino acids contacting DNA major grooves.
Purpose of the Study:
- To review DNA recognition mechanisms by Cys2His2 zinc fingers.
- To summarize advancements in engineering novel DNA-binding proteins with specificities using selected zinc fingers.
Main Methods:
- Analysis of DNA recognition by Cys2His2 zinc fingers.
- Review of studies involving phage display for selecting zinc fingers with new specificities.
Main Results:
- Zinc finger proteins offer a modular framework for designing novel DNA-binding proteins due to their diverse sequence recognition capabilities.
- Recurring patterns in side chain-base interactions have been observed, but a universal "recognition code" for optimal protein design is lacking.
- Interactions between adjacent fingers and linker regions complicate the construction of multi-finger proteins.
Conclusions:
- Designing artificial DNA-binding proteins based on Cys2His2 zinc fingers is feasible but complex.
- Phage display is a valuable tool for generating zinc fingers with tailored DNA specificities.
- Further research into the intricate structural details of zinc finger-DNA recognition is needed for predictable protein design.
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