Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 36, Pages 13403-13408Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0802113105
Keywords
denatured state ensemble; FRET and SAXS experiments; protein L; cold shock protein; protein collapse
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Funding
- National Science Foundation [05-14056]
- US-Israeli Binational Science Foundation [2002371]
- National Institutes of Health [1 R01GM080515]
- National Institutes of Health GPP Biophysics Fellowship
- Intramural Research Program of the National Heart, Lung, and Blood Institute of the National Institutes of Health
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Interactions between denaturants and proteins are commonly used to probe the structures of the denatured state ensemble and their stabilities. Osmolytes, a class of small intracellular organic molecules found in all taxa, also profoundly affect the equilibrium properties of proteins. We introduce the molecular transfer model, which combines simulations in the absence of denaturants or osmolytes, and Tanford's transfer model to predict the dependence of equilibrium properties of proteins at finite concentration of osmolytes. The calculated changes in the thermodynamic quantities (probability of being in the native basin of attraction, m values, FRET efficiency, and structures of the denatured state ensemble) with GdmCl concentration [C] for the protein L and cold shock protein CspTm compare well with experiments. The radii of gyration of the subpopulation of unfolded molecules for both proteins decrease (i.e., they undergo a collapse transition) as [C] decreases. Although global folding is cooperative, residual secondary structures persist at high denaturant concentrations. The temperature dependence of the specific heat shows that the folding temperature (T-F) changes linearly as urea and trimethylamine N-oxide (TMAO) concentrations increase. The increase in TF in TIVIAO can be as large as 20 degrees C, whereas urea decreases TF by as much as 35 degrees C. The stabilities of protein L and CspTm also increase linearly with the concentration of osmolytes (proline, sorbitol, sucrose, TMAO, and sarcosine).
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