• San Hadzi
  • Andrej Mernik
  • Crtomir Podlipnik
  • Remy Loris
  • Jurij Lah
Many intrinsically disordered proteins (IDP) that fold upon binding retain conformational heterogeneity in IDP-target complexes. The thermodynamics of such fuzzy interactions is poorly understood. Here we introduce a thermodynamic framework, based on analysis of ITC and CD spectroscopy data, that provides experimental description of IDP association in terms of folding and binding contributions which can be predicted using sequence folding propensities and molecular modeling. We show how IDP can modulate the entropy and enthalpy by adapting their bound-state structural ensemble to achieve optimal binding. This is explained in terms of a free energy landscape that provides the relationship between free energy, sequence folding propensity and disorder. The observed "fuzzy" behavior is possible not only because of IDP flexibility but also because backbone and side chain interactions are, to some extent, energetically decoupled allowing IDP to minimize energetically unfavorable folding.
Original languageEnglish
Pages (from-to)14494-14497
Number of pages4
JournalAngew. Chem. Int. Ed.
Issue number46
Publication statusPublished - 15 Sep 2017

    Research areas

  • Biophysics, Molecular biophysics, Toxin-Antitoxin module, Thermodynamics, intrinsically disordered protein, intrinsically disordered protein segment, Fuzzy interaction, Persistence

ID: 34659040