Osmolyte effects on protein stability and solubility: A balancing act between backbone and side-chains

Matthew Auton, Jörg Rösgen, Mikhail Sinev, Luis Marcelo F. Holthauzen, D. Wayne Bolen

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

In adaptation biology the discovery of intracellular osmolyte molecules that in some cases reach molar levels, raises questions of how they influence protein thermodynamics. We've addressed such questions using the premise that from atomic coordinates, the transfer free energy of a native protein (ΔG tr, N) can be predicted by summing measured water-to-osmolyte transfer free energies of the protein's solvent exposed side chain and backbone component parts. ΔG tr, D is predicted using a self avoiding random coil model for the protein, and ΔG tr, D - ΔG tr, N, predicts the m-value, a quantity that measures the osmolyte effect on the N D transition. Using literature and newly measured m-values we show 1:1 correspondence between predicted and measured m-values covering a range of 12 kcal/mol/M in protein stability for 46 proteins and 9 different osmolytes. Osmolytes present a range of side chain and backbone effects on N and D solubility and protein stability key to their biological roles.

Original languageEnglish (US)
Pages (from-to)90-99
Number of pages10
JournalBiophysical Chemistry
Volume159
Issue number1
DOIs
StatePublished - Nov 2011

Keywords

  • Folding
  • Osmolyte
  • Protein stability
  • Solubility
  • Urea
  • m-Value

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Organic Chemistry

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