Structural Specificity of Peptides in Z-DNA Formation and Energetics of the Peptide-induced B—Z Transition of Poly(dG-m 5dC)

Abstract

The effects of oligopeptide binding in the conformation of double-stranded poly(dG-m 5dC) have been examined by circular dichroism spectroscopy. Conversion from the right-handed B-form to the left-handed Z-form occurs very efficiently in the presence of peptides having amino acid sequences of the (Lys-X) n -Lys type, where X is a non-bulky amino acid residue such as Gly, Ala and Lys. The ability to induce the B—Z transition increases rapidly with increasing repeat number n, and the peptide with n = 2—3 readily convert the B-form DNA to the Z -form at a peptide/nucleotide molar ratio of 0·06 to 0·8 (one peptide per 13 to 17 nucleotides). The peptide-induced B—Z transition of poly(dG-m 5dC) duplexes takes place even at a physiological salt concentration (150 mM NaCl). The activation energy and van't Hoff enthalpy of the B—Z conversion have been determined to be 124(±7) and 138(±12)kJ/mol, respectively, for the (Lys-Gly) 2-Lys-induced transition. The van't Hoff enthalpy of the peptide-induced B—Z transition is particularly small compared to those of the transitions caused by other inducers. The large enthalpic contribution to the Z-DNA formation indicates that the peptide binds preferentially to the Z-arranged DNA phosphate groups and stabilizes the Z -stretch significantly. It is pointed out that some DNA-binding proteins have amino acid sequences that favor Z-DNA.