Aggregation of Intrinsically Disordered Proteins: An Investigation of the Behavior of Stathmin Aggregated in the Presence of Ficoll 70 and 1,4-Dioxane
Author:Ashley J. Chui
Mentor:Michael D. Bridges, Assistant Professor of Chemistry, California State University Fullerton
Proteins that lack a three-dimensional fold, recently classified as ‘intrinsically disordered proteins’ (IDPs), have been shown to play vital roles in binding recognition, cellular regulation, and signal transduction processes. The misfolding or unfolding of these highly flexible and dynamic proteins often leads to their consolidation into “aggregate plaques,” which have been connected to various illnesses, including Parkinson’s disease and Alzheimer’s disease. As an IDP, stathmin is a regulatory protein involved in the maintenance of cytoskeletal microtubules. Although stathmin proves to be highly flexible and essentially unfolded in solution, it has not been shown to be a pathogenically aggregating protein. Because stathmin is a relatively easy IDP with which to work in the laboratory, we have studied its aggregation behavior as a model IDP system, investigating the effects of Ficoll 70 (a macromolecular crowding agent) and 1,4-dioxane (a modifier of the hydrophobic effect). This was done in order to test our prediction that stathmin aggregates due to the crowdedness of the environment or because of the water-solubility of stathmin, and this aggregation is reversible upon a return to favorable solution conditions. Light-scattering data indicate that there exists a ‘critical concentration’ dependent aggregation solubilization equilibrium for stathmin, but that aggregate formation may not be completely reversible. This study of aggregation reversibility of stathmin as a model system could assist in our understanding of how other pathogenically aggregating proteins behave on the molecular level.