Synergy in Protein–Osmolyte Mixtures

Virtually all taxa use osmolytes to protect cells against biochemical stress. Osmolytes often occur in mixtures, such as the classical combination of urea with TMAO (trimethylamine N-oxide) in cartilaginous fish or the cocktail of at least six different osmolytes in the kidney. The concentration pat...

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Bibliographic Details
Published in:The journal of physical chemistry. B 2015-01, Vol.119 (1), p.150-157
Main Author: Rosgen, Jorg
Format: Article
Language:English
Subjects:
Biomedical materials
Kidneys
Methylamines - chemistry
Models, Statistical
Notches
Osmolar Concentration
Proteins
Proteins - chemistry
Solvation
Surface chemistry
Surface Properties
Surgical implants
Thermodynamics
Urea - chemistry
Ureas
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Summary:Virtually all taxa use osmolytes to protect cells against biochemical stress. Osmolytes often occur in mixtures, such as the classical combination of urea with TMAO (trimethylamine N-oxide) in cartilaginous fish or the cocktail of at least six different osmolytes in the kidney. The concentration patterns of osmolyte mixtures found in vivo make it likely that synergy between them plays an important role. Using statistical mechanical n-component Kirkwood–Buff theory, we show from first principles that synergy in protein–osmolyte systems can arise from two separable sources: (1) mutual alteration of protein surface solvation and (2) effects mediated through bulk osmolyte chemical activities. We illustrate both effects in a four-component system with the experimental example of the unfolding of a notch ankyrin domain in urea–TMAO mixtures, which make urea a less effective denaturant and TMAO a more effective stabilizer. Protein surface effects are primarily responsible for this synergy. The specific patterns of surface solvation point to denatured state expansion as the main factor, as opposed to direct competition.
ISSN:1520-6106
1520-5207
DOI:10.1021/jp5111339