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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TL;DR: In this article, a review of TF-mediated gene regulation, discuss successful targeting strategies and highlight ongoing challenges and emerging approaches to address them, as well as several emerging approaches for TF-targeting.
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The molecular basis for cellular function of intrinsically disordered protein regions.
TL;DR: The biochemical and biophysical foundations that underlie how and why disordered regions can engage in productive cellular functions are considered, examples of emerging concepts are provided and how protein disorder contributes to intracellular information processing and regulation of cellular function is discussed.
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Sequence Effects on Size, Shape, and Structural Heterogeneity in Intrinsically Disordered Proteins.
TL;DR: Cl clustering analysis reveals that the menagerie of structures explored by IDPs is diverse, with the extent of heterogeneity being highly sequence-dependent, even though ensemble-averaged properties, such as the dependence of Rg on chain length, may suggest synthetic polymer-like behavior in a good solvent.
Conformational Ensembles of an Intrinsically Disordered Protein Consistent with NMR, SAXS, and Single-Molecule FRET.
Gregory-Neal W. Gomes,Mickael Krzeminski,Ashley Namini,Erik W. Martin,Tanja Mittag,Teresa Head-Gordon,Julie D. Forman-Kay,Claudiu C. Gradinaru +7 more
TL;DR: From the experimentally well supported ensembles, it is found they are consistent with independent biophysical models of Sic1's ultrasensitive binding to its partner Cdc4, and underscores the importance of integrative modelling and validation in calculating and drawing biological conclusions from IDP conformationalEnsembles.
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Effective concentrations enforced by intrinsically disordered linkers are governed by polymer physics.
TL;DR: The system developed here provides a strategy to systematically investigate the relationship between sequence and compaction of intrinsically disordered proteins, and shows that effective concentrations follow simple geometric models based on polymer physics, offering an indirect method to probe the structural properties of the linker.
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