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Science 17 August 1990:
Vol. 249. no. 4970, pp. 774 - 778
DOI: 10.1126/science.2389143
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Articles

Science, Vol 249, Issue 4970, 774-778
Copyright © 1990 by American Association for the Advancement of Science

articles

Design of DNA-binding peptides based on the leucine zipper motif

KT O'Neil, RH Hoess, and WF DeGrado

Central Research and Development Department, E.I. du Pont de Nemours & Co., Wilmington, DE 19880-0328.

A class of transcriptional regulator proteins bind to DNA at dyad-symmetric sites through a motif consisting of (i) a "leucine zipper" sequence that associates into noncovalent, parallel, alpha-helical dimers and (ii) a covalently connected basic region necessary for binding DNA. The basic regions are predicted to be disordered in the absence of DNA and to form alpha helices when bound to DNA. These helices bind in the major groove forming multiple hydrogen-bonded and van der Waals contacts with the nucleotide bases. To test this model, two peptides were designed that were identical to natural leucine zipper proteins only at positions hypothesized to be critical for dimerization and DNA recognition. The peptides form dimers that bind specifically to DNA with their basic regions in alpha-helical conformations.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)