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Chemphyschem. 2018 Sep 18;19(18):2290-2294. doi: 10.1002/cphc.201800534. Epub 2018 Jun 21.

Non-Steric Interactions Predict the Trend and Steric Interactions the Offset of Protein Stability in Cells.

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Department of Chemistry and Department of Physics, University of Illinois at Urbana-Champaign Urbana, Illinois, 61801, United States.
Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign Urbana, Illinois, 61801, United States.


Although biomolecules evolved to function in the cell, most biochemical assays are carried out in vitro. In-cell studies highlight how steric and non-steric interactions modulate protein folding and interactions. VlsE and PGK present two extremes of chemical behavior in the cell: the extracellular protein VlsE is destabilized in eukaryotic cells, whereas the cytoplasmic protein PGK is stabilized. VlsE and PGK are benchmarks in a systematic series of solvation environments to distinguish contributions from non-steric and steric interactions to protein stability, compactness, and folding rate by comparing cell lysate, a crowding agent, ionic buffer and lysate buffer with in-cell results. As anticipated, crowding stabilizes proteins, causes compaction, and can speed folding. Protein flexibility determines its sensitivity to steric interactions or crowding. Non-steric interactions alone predict in-cell stability trends, while crowding provides an offset towards greater stabilization. We suggest that a simple combination of lysis buffer and Ficoll is an effective new in vitro mimic of the intracellular environment on protein folding and stability.


FRET; laser-induced temperature-jump; macromolecular crowding; protein folding; quinary interactions

[Indexed for MEDLINE]

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