Hofmeister Effects and Amyloid Structure of Sup35

Prion proteins are capable of converting from their soluble, biologically-functional forms into highly ordered, fibrous aggregates, called amyloids. This conversion is associated with certain neurodegenerative conditions, such as Alzheimer's disease. Protein misfolding is strongly influenced by ion-specific solvent effects, known as Hofmeister effects. Using a yeast prion protein (Sup35), we tested the influence of a host of sodium salts on aggregation kinetics and investigated the aggregates that were formed. Aggregation kinetics was starkly different between the two main groups of salts (chaotropes and kosmotropes). The differences in aggregation kinetics profoundly effected the structures of the resulting aggregates. These structural differences were investigated by studying the amyloids’ physical stability, thermostability, fiber length distributions, infectivity and TEM images. The fastest forming aggregates were found to be the most fragment prone, least thermostable, shortest, most infectious, and least orders when imaged. The opposite was true of slower forming aggregates. These findings are in line with previous works on temperature effects on Sup35 and what one might expect for a non-specific colloidal system. This work shows the profound effect of solvents and ion-specific/hydration effects on aggregation and disease.