Structure of a Designed Dimeric Zinc Finger Protein Bound to DNA,
- 30 October 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 42 (46) , 13401-13409
- https://doi.org/10.1021/bi034830b
Abstract
Proteins that employ dimerization domains to bind cooperatively to DNA have a number of potential advantages over monomers with regards to gene regulation. Using a combination of structure-based design and phage display, a dimeric Cys2His2 zinc finger protein has been created that binds cooperatively to DNA via an attached leucine zipper dimerization domain. This chimera, derived from components of Zif268 and GCN4, displayed excellent DNA-binding specificity, and we now report the 1.5 Å resolution cocrystal structure of the Zif268-GCN4 homodimer bound to DNA. This structure shows how phage display has annealed the DNA binding and dimerization domains into a single functional unit. Moreover, this chimera provides a potential platform for the creation heterodimeric zinc finger proteins that can regulate a desired target gene through cooperative DNA recognition.Keywords
This publication has 10 references indexed in Scilit:
- Engineering polydactyl zinc-finger transcription factorsNature Biotechnology, 2002
- A standard reference frame for the description of nucleic acid base-pair geometryJournal of Molecular Biology, 2001
- DNA Recognition by Cys2His2 Zinc Finger ProteinsAnnual Review of Biophysics, 2000
- Binding Studies with Mutants of Zif268Journal of Biological Chemistry, 1999
- Toward controlling gene expression at will: Selection and design of zinc finger domains recognizing each of the 5′-GNN-3′ DNA target sequencesProceedings of the National Academy of Sciences, 1999
- Toward controlling gene expression at will: Specific regulation of the erbB - 2 / HER - 2 promoter by using polydactyl zinc finger proteins constructed from modular building blocksProceedings of the National Academy of Sciences, 1998
- Jury still undecided on French reformsNature, 1998
- Design of polydactyl zinc-finger proteins for unique addressing within complex genomesProceedings of the National Academy of Sciences, 1997
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994
- Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modulesCell, 1994