Journal Article

Temperature-dependent solvation modulates the dimensions of disordered proteins

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

2014

Overview

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

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Amino acids / Biological Sciences / Energy transfer / Environmental conditions / environmental factors / Fluorescence Resonance Energy Transfer / Free energy / Gyration / High temperature / hydrophilicity / Hydrophobic and Hydrophilic Interactions / hydrophobicity / Molecules / Physical Sciences / Polymers / Protein Conformation / Protein Unfolding / Proteins / Simulation / Solubility / Solvation / Solvents / Temperature / Temperature dependence / Thermodynamics