Temperature-dependent solvation modulates the dimensions of disordered proteins

Rene Wuttke, Hagen Hofmann, Daniel Nettels, Madeleine B. Borgia, Jeetain Mittal, Robert B. Best, Benjamin Schuler

Research output: Contribution to journalArticlepeer-review


For disordered proteins, the dimensions of the chain are an important property that is sensitive to environmental conditions. We have used single-molecule Forster resonance energy transfer to probe the temperature-induced chain collapse of five unfolded or intrinsically disordered proteins. Because this behavior is sensitive to the details of intrachain and chain-solvent interactions, the collapse allows us to probe the physical interactions governing the dimensions of disordered proteins. We find that each of the proteins undergoes a collapse with increasing temperature, with the most hydrophobic one, lambda-repressor, undergoing a reexpansion at the highest temperatures. Although such a collapse might be expected due to the temperature dependence of the classical "hydrophobic effect," remarkably we find that the largest collapse occurs for the most hydrophilic, charged sequences. Using a combination of theory and simulation, we show that this result can be rationalized in terms of the temperature-dependent solvation free energies of the constituent amino acids, with the solvation properties of the most hydrophilic residues playing a large part in determining the collapse.
Original languageEnglish
Pages (from-to)5213-5218
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number14
StatePublished - Apr 2014


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