title: Stimuli-responsive selection of target DNA sequences by synthetic bZIP peptides.
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.
authors.affiliation: Departamento de Química Orgánica and Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Mosquera
authors.forename: Adrián
authors.initials: A
authors.lastname: Jiménez-Balsa
authors.forename: Verónica I
authors.initials: VI
authors.lastname: Dodero
authors.forename: M Eugenio
authors.initials: ME
authors.lastname: Vázquez
authors.forename: José L
authors.initials: JL
authors.lastname: Mascareñas
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D024202:Electrophoretic Mobility Shift Assay; D005454:Fluorescence Polarization; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D010455:Peptides