Stimuli-responsive selection of target DNA sequences by synthetic bZIP peptides

Jesús Mosquera, Adrián Jiménez-Balsa, Verónica I. Dodero, M. Eugenio Vázquez, Josél L. Mascareñas

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

One of the strategies used by nature to regulate gene expression relies on the stimuli-controlled combination of DNA-binding proteins. This in turn determines the target-binding site within the genome, and thereby whether a particular gene is activated or repressed. Here we demonstrate how a designed basic region leucine zipper-based peptide can be directed towards two different DNA sequences depending on its dimerization arrangement. While the monomeric peptide is non-functional, a C-terminal metallo-dimer recognizes the natural ATF/CREB-binding site (5′-ATGA cg TCAT-3′), and a N-terminal disulphide dimer binds preferentially to the swapped sequence (5′-TCAT cg ATGA-3′). As the dimerization mode can be efficiently controlled by appropriate external reagents, it is possible to reversibly drive the peptide to either DNA site in response to such specific inputs. This represents the first example of a designed molecule that can bind to more than one specific DNA sequence depending on changes in its environment.

Original languageEnglish
Article number1874
Number of pages8
JournalNature Communications
Volume4
DOIs
Publication statusPublished - 21 May 2013

Keywords

  • gene expression
  • DNA-binding proteins
  • synthetic bZIP peptides

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    Mosquera, J., Jiménez-Balsa, A., Dodero, V. I., Vázquez, M. E., & Mascareñas, J. L. (2013). Stimuli-responsive selection of target DNA sequences by synthetic bZIP peptides. Nature Communications, 4, [1874]. https://doi.org/10.1038/ncomms2825