Temperature-dependent solvation modulates the dimensions of disordered proteins. Academic Article uri icon


  • For disordered proteins, the dimensions of the chain are an important property that is sensitive to environmental conditions. We have used single-molecule Frster 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, -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.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 51.5

author list (cited authors)

  • Wuttke, R., Hofmann, H., Nettels, D., Borgia, M. B., Mittal, J., Best, R. B., & Schuler, B.

citation count

  • 134

complete list of authors

  • Wuttke, René||Hofmann, Hagen||Nettels, Daniel||Borgia, Madeleine B||Mittal, Jeetain||Best, Robert B||Schuler, Benjamin

publication date

  • April 2014