Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water
Joshua A. Riback,Micayla A. Bowman,Adam M. Zmyslowski,Catherine R. Knoverek,John M. Jumper,James R. Hinshaw,Emily B. Kaye,Karl F. Freed,Patricia L. Clark,Tobin R. Sosnick +9 more
TL;DR: The results suggest that the unfolded state of most foldable sequences is expanded; it is conjecture that this property was selected by evolution to minimize misfolding and aggregation.
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Abstract: 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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Citations
Valence and patterning of aromatic residues determine the phase behavior of prion-like domains
Erik W. Martin,Alex S. Holehouse,Ivan Peran,Mina Farag,J. Jeremías Incicco,Anne Bremer,Christy R. Grace,Andrea Soranno,Rohit V. Pappu,Tanja Mittag +9 more
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Sequence determinants of protein phase behavior from a coarse-grained model.
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Biomolecular Phase Separation: From Molecular Driving Forces to Macroscopic Properties
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Relation between single-molecule properties and phase behavior of intrinsically disordered proteins
TL;DR: The results show that these characteristic temperatures are highly correlated, suggesting that experiments performed in dilute conditions may be used to predict phase separation, and suggest that smaller simulations or experiments to determine Tθ or TB can provide useful insights into the corresponding phase behavior.
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Accurate model of liquid-liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties.
TL;DR: In this article, a coarse-grained model of intrinsically disordered proteins (IDPs) with residue-level detail was developed based on an extensive set of experimental data on single-chain properties.
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