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Science 17 August 1990:
Vol. 249. no. 4970, pp. 769 - 771
DOI: 10.1126/science.2389142
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Articles

Science, Vol 249, Issue 4970, 769-771
Copyright © 1990 by American Association for the Advancement of Science

articles

Sequence-specific DNA binding by a short peptide dimer

RV Talanian, CJ McKnight, and PS Kim

Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142.

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for the basic region of the yeast transcriptional activator GCN4 has been developed in which the leucine zipper has been replaced by a disulfide bond.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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