title: Sequence-specific DNA binding by a short peptide dimer.
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for the basic region of the yeast transcriptional activator GCN4 has been developed in which the leucine zipper has been replaced by a disulfide bond.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.
authors.affiliation: Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142.
authors.forename: R V
authors.initials: RV
authors.lastname: Talanian
authors.forename: C J
authors.initials: CJ
authors.lastname: McKnight
authors.forename: P S
authors.initials: PS
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003850:Deoxyribonuclease I; D004220:Disulfides; D005656:Fungal Proteins / Q000378:metabolism*; D007930:Leucine; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011487:Protein Conformation; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D004220:Disulfides; D005656:Fungal Proteins; D046911:Macromolecular Substances; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA; D011494:Protein Kinases; D003850:Deoxyribonuclease I; D007930:Leucine