Insights into the Molecular Recognition of the 5’-GNN-3Family of DNA Sequences by Zinc Finger Domains

 

April 29, 2004

Chien Kuo Yuan

 

Abstract

The goal of this study was to investigate zinc finger recognition of the 16-member family of 5-GNN-3DNA sequences in order to understand better zinc finger/DNA-binding mechanisms. Phage-display studies and the rational design of mutant zinc finger domains were used to accomplish this goal. A total of 84 mutants of a three-domain zinc finger protein have been analyzed for their DNA-binding specificity. We report the results of mutagenesis experiments and obtain new insights into zinc finger/DNA interactions from combining specificity data with computer modeling and comparison with known structural data from NMR and crystallographic studies. We may get some information that the orientation of the recognition helix relative to the DNA is a critical determinant of specificity. However, it is clear that zinc finger recognition of DNA is substantially more complex than a simple one to one amino acid to base code.

 

Source

      J Mol Biol. 2000 Nov 3;303(4):489-502.

        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=11054286&dopt=Abstract

 

 

Reference

1.           Segal, D. J., Dreier, B., Beerli, R. R. & Barbas, C. F., III (1999). Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5-GNN-3DNA target sequences. Proc. Natl Acad. Sci. USA, 96, 2758-2763.

2.           Introduction to Protein Structure 2ed edition , Carl Branden & John Tooze