Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water

Science. 2017 Oct 13;358(6360):238-241. doi: 10.1126/science.aan5774.


A substantial fraction of the proteome is intrinsically disordered, and even well-folded proteins adopt non-native geometries during synthesis, folding, transport, and turnover. Characterization of intrinsically disordered proteins (IDPs) is challenging, in part because of a lack of accurate physical models and the difficulty of interpreting experimental results. We have developed a general method to extract the dimensions and solvent quality (self-interactions) of IDPs from a single small-angle x-ray scattering measurement. We applied this procedure to a variety of IDPs and found that even IDPs with low net charge and high hydrophobicity remain highly expanded in water, contrary to the general expectation that protein-like sequences collapse in water. Our results suggest that the unfolded state of most foldable sequences is expanded; we conjecture that this property was selected by evolution to minimize misfolding and aggregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Intrinsically Disordered Proteins / chemistry*
  • Protein Conformation, alpha-Helical
  • Protein Domains
  • Protein Folding*
  • Scattering, Small Angle*
  • Virulence Factors, Bordetella / chemistry
  • Water / chemistry*
  • X-Ray Diffraction / methods*


  • Bacterial Outer Membrane Proteins
  • Intrinsically Disordered Proteins
  • Virulence Factors, Bordetella
  • Water
  • pertactin