title: Protein unfolding in detergents: effect of micelle structure, ionic strength, pH, and temperature.
abstract: The 101-residue monomeric protein S6 unfolds in the anionic detergent sodium dodecyl sulfate (SDS) above the critical micelle concentration, with unfolding rates varying according to two different modes. Our group has proposed that spherical micelles lead to saturation kinetics in unfolding (mode 1), while cylindrical micelles prevalent at higher SDS concentrations induce a power-law dependent increase in the unfolding rate (mode 2). Here I investigate in more detail how micellar properties affect protein unfolding. High NaCl concentrations, which induce cylindrical micelles, favor mode 2. This is consistent with our model, though other effects such as electrostatic screening cannot be discounted. Furthermore, unfolding does not occur in mode 2 in the cationic detergent LTAB, which is unable to form cylindrical micelles. A strong retardation of unfolding occurs at higher LTAB concentrations, possibly due to the formation of dead-end protein-detergent complexes. A similar, albeit much weaker, effect is seen in SDS in the absence of salt. Chymotrypsin inhibitor 2 exhibits the same modes of unfolding in SDS as S6, indicating that this type of protein unfolding is not specific for S6. The unfolding process in mode 1 has an activation barrier similar in magnitude to that in water, while the activation barrier in mode 2 is strongly concentration-dependent. The strong pH-dependence of unfolding in SDS and LTAB suggests that the rate of unfolding in anionic detergent is modulated by repulsion between detergent headgroups and anionic side chains, while cationic side chains modulate unfolding rates in cationic detergents.
mesh_terms: D055592:Biophysical Phenomena; D001703:Biophysics; D002412:Cations; D003902:Detergents / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007700:Kinetics; D008823:Micelles; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry; D010940:Plant Proteins; D011489:Protein Denaturation; D017510:Protein Folding; D038601:Ribosomal Protein S6 / Q000737:chemistry; D012965:Sodium Chloride / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013696:Temperature; D016963:Thermus thermophilus / Q000378:metabolism
chemical_list: D002412:Cations; D003902:Detergents; D007477:Ions; D008823:Micelles; D010455:Peptides; D010940:Plant Proteins; D038601:Ribosomal Protein S6; C093336:chymotrypsin inhibitor 2; D012967:Sodium Dodecyl Sulfate; D012965:Sodium Chloride