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

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Science  13 Oct 2017:
Vol. 358, Issue 6360, pp. 238-241
DOI: 10.1126/science.aan5774

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An expanded view of disordered proteins

Disordered proteins sample an ensemble of conformations, but it has remained unclear how compact these conformations are in water. Polymer physics relates the radius of gyration (Rg) to solvent quality, with more chain collapse occurring in poorer solvents. Riback et al. developed an analysis scheme that allows them to extract solvent quality and Rg from a single small-angle x-ray scattering measurement. Applying this method, they found that even disordered proteins with low net charge and high hydrophobicity remain expanded in water.

Science, this issue p. 238


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.

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