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PubMed · 2389142

Sequence-specific DNA binding by a short peptide dimer.

R V Talanian·C J McKnight·P S Kim
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Abstract

A recently described class of DNA binding proteins is characterized by the "bZIP" motif, which consists of a basic region that contacts DNA and an adjacent "leucine zipper" that mediates protein dimerization. A peptide model for the basic region of the yeast transcriptional activator GCN4 has been developed in which the leucine zipper has been replaced by a disulfide bond. The 34-residue peptide dimer, but not the reduced monomer, binds DNA with nanomolar affinity at 4 degrees C. DNA binding is sequence-specific as judged by deoxyribonuclease I footprinting. Circular dichroism spectroscopy suggests that the peptide adopts a helical structure when bound to DNA. These results demonstrate directly that the GCN4 basic region is sufficient for sequence-specific DNA binding and suggest that a major function of the GCN4 leucine zipper is simply to mediate protein dimerization. Our approach provides a strategy for the design of short sequence-specific DNA binding peptides.

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Amino Acid SequenceBase SequenceBinding SitesCircular DichroismDNADNA-Binding ProteinsDeoxyribonuclease IDisulfidesFungal ProteinsLeucineMacromolecular SubstancesMolecular Sequence DataPeptidesProtein ConformationProtein KinasesSaccharomyces cerevisiae ProteinsTranscription FactorsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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R V Talanian, C J McKnight, P S Kim. 1990-08-17. Sequence-specific DNA binding by a short peptide dimer.. https://doi.org/10.1126/science.2389142

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