期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：36
页码：13403-13408
DOI：10.1073/pnas.0802113105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 (TF) changes linearly as urea and trimethylamine N-oxide (TMAO) concentrations increase. The increase in TF in TMAO 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).
关键词：denatured state ensemble ; FRET and SAXS experiments ; protein L ; cold shock protein ; protein collapse
