Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein

Sci Rep. 2016 Feb 25;6:21994. doi: 10.1038/srep21994.


Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this 'folding upon binding' process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb (c-Myb) upon binding its partner KIX. By determining the structure of the folding transition state for the binding of wild-type and three mutational variants of KIX, we found a remarkable plasticity of the folding pathway of c-Myb. To explain this phenomenon, we show that the folding of c-Myb is templated by the structure of KIX. This adaptive folding behaviour, which occurs by heterogeneous nucleation, differs from the robust homogeneous nucleation typically observed for globular proteins. We suggest that this templated folding mechanism may enable intrinsically disordered proteins to achieve specific and reliable binding with multiple partners while avoiding aberrant interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Intrinsically Disordered Proteins / chemistry*
  • Intrinsically Disordered Proteins / metabolism
  • Models, Molecular*
  • Protein Binding
  • Protein Conformation
  • Protein Folding*
  • Proto-Oncogene Proteins c-myb / chemistry
  • Proto-Oncogene Proteins c-myb / metabolism
  • Reproducibility of Results


  • Carrier Proteins
  • Intrinsically Disordered Proteins
  • Proto-Oncogene Proteins c-myb