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

Caitlin M. Davis, Martin Gruebele

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2290-2294
Number of pages5
JournalChemPhysChem
Volume19
Issue number18
DOIs
StatePublished - Sep 18 2018

Keywords

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

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Physical and Theoretical Chemistry

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