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Deconstruction of GCN4/GCRE into a monomeric peptide-DNA complex

Nature Structural Biology volume 2, pages 450–457 (1995)Cite this article

Abstract

Here we describe a system that enables short peptides to bind DNA sequence-specifically. Linking the peptide covalently to DNA through a disulphide bond eliminates the unfavourable energetic cost of diffusion and thus potentiates the peptide-DNA interaction. By this approach we have deconstructed the GCN4/DNA complex into its elemental DNA recognition units. We find that the GCN4 basic region contacts the two half-sites with very different affinities and propose that this thermodynamic asymmetry plays a role in differential regulation of gene expression. Specific binding of the peptide to DNA stabilizes the disulphide bond toward reduction suggesting a novel approach to the discovery of new DNA-binding specificities.

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Authors and Affiliations

  1. Department of Chemistry, Harvard University, Cambridge, Massachusetts, 02138, USA

    Dusan Stanojevic & Gregory L. Verdine

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  1. Dusan Stanojevic
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  2. Gregory L. Verdine
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Stanojevic, D., Verdine, G. Deconstruction of GCN4/GCRE into a monomeric peptide-DNA complex. Nat Struct Mol Biol 2, 450–457 (1995). https://doi.org/10.1038/nsb0695-450

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