Research Repository

Thermodynamic analysis of Jun-Fos coiled coil peptide antagonists

Worrall, JAR and Mason, JM (2011) 'Thermodynamic analysis of Jun-Fos coiled coil peptide antagonists.' FEBS Journal, 278 (4). 663 - 672. ISSN 1742-464X

Full text not available from this repository.

Abstract

Dimerization of the Jun-Fos activator protein-1 (AP-1) transcriptional regulator is mediated by coiled coil regions that facilitate binding of the basic regions to a specific promoter. AP-1 is responsible for the regulation of a number of genes involved in cell proliferation. We have previously derived peptide antagonists and demonstrated them to be capable of binding to the Jun or Fos coiled coil region with high affinity (KD values in the low nm range relative to μm for the wild-type interaction). Use of isothermal titration calorimetry combined with CD spectroscopy is reported to elucidate the thermodynamic parameters that drive the interaction stability of peptide antagonists with their cJun and cFos targets. We observe that the free energy of binding for antagonist-target complexes is dominated by the enthalpic term, is opposed by unfavourable entropic contributions consistent with reduced conformational freedom and that these values in turn correlate well (r = -0.97) with the measured helicity of each dimeric pair. The more helical the antagonist-target complex, the more favourable the change in enthalpy, which is in turn opposed more strongly by entropy. Antagonistic peptides are predicted to represent excellent scaffolds for further refinement. By contrast, the wild-type cJun-cFos complex is dominated by a favourable entropic contribution, owing partially to a decrease in buried hydrophobic groups from cFos core residues and an increase in the conformational freedom. © 2011 The Authors Journal compilation © 2011 FEBS.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Admin
Date Deposited: 04 Aug 2011 15:07
Last Modified: 20 Nov 2019 11:15
URI: http://repository.essex.ac.uk/id/eprint/382

Actions (login required)

View Item View Item