Dataset Information

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

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.

SUBMITTER: Riback JA

PROVIDER: S-EPMC5959285 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Riback Joshua A JA Bowman Micayla A MA Zmyslowski Adam M AM Knoverek Catherine R CR Jumper John M JM Hinshaw James R JR Kaye Emily B EB Freed Karl F KF Clark Patricia L PL Sosnick Tobin R TR

Science (New York, N.Y.) 20171001 6360

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 ...[more]

PMID: 29026044

Similar Datasets

Project description:Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) play important roles in many aspects of normal cell physiology, such as signal transduction and transcription, as well as pathological states, including Alzheimer's, Parkinson's, and Huntington's disease. Unlike their globular counterparts that are defined by a few structures and free energy minima, IDP/IDR comprise a large ensemble of rapidly interconverting structures and a corresponding free energy landscape characterized by multiple minima. This aspect has precluded the use of structural biological techniques, such as X-ray crystallography and nuclear magnetic resonance (NMR) for resolving their structures. Instead, low-resolution techniques, such as small-angle X-ray or neutron scattering (SAXS/SANS), have become a mainstay in characterizing coarse features of the ensemble of structures. These are typically complemented with NMR data if possible or computational techniques, such as atomistic molecular dynamics, to further resolve the underlying ensemble of structures. However, over the past 10-15 years, it has become evident that the classical, pairwise-additive force fields that have enjoyed a high degree of success for globular proteins have been somewhat limited in modeling IDP/IDR structures that agree with experiment. There has thus been a significant effort to rehabilitate these models to obtain better agreement with experiment, typically done by optimizing parameters in a piecewise fashion. In this work, we take a different approach by optimizing a set of force field parameters simultaneously, using machine learning to adapt force field parameters to experimental SAXS scattering profiles. We demonstrate our approach in modeling three biologically IDP ensembles based on experimental SAXS profiles and show that our optimization approach significantly improve force field parameters that generate ensembles in better agreement with experiment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets