(7b) Hofmeister Effects On Sup35NM Amyloid Formation Kinetics

Authors: 
Rubin, J., Georgia Institute of Technology
Behrens, S. H., Georgia Institute of Technology
Chernoff, Y. O., Georgia Institute of Technology
Bommarius, A. S., Georgia Institute of Technology


The addition of salt to a colloidal dispersion reduces the energetic barrier for aggregation; however, in the context of protein, salts do not all have the same effect. The Hofmeister series is a qualitative ranking system for ions describing the extent to which an ion will affect a variety of phenomena in solution including (but not limited to) protein solubility, enzyme activity, and colloidal stability. Since protein stability plays an important role in protein misfolding diseases, we test the influence of a host of Hofmeister salts on the aggregation rate of Sup35NM, a model yeast prion protein. Prion proteins are capable of converting from their soluble forms into highly ordered fibrous cross-β aggregates, known as amyloids. This conversion is associated with certain neurodegenerative conditions in mammals, such as Alzheimer disease, and controls heritable phenotypes in yeast. Previously we have studied Sup35NM aggregation in the presence of select anions using the Congo red binding assay and found an inverse Hofmeister trend, where chaotropes strongly stabilize and kosmotropes destabilize. This study confirmed that result and expands on the topic by examining the effect of a wide range of both anions and cations at varying concentrations on the aggregation rate, lag time prior to aggregation and the extent of aggregation of Sup35NM using the fluorescent amyloid binding dye, thioflavine T. We found significant concentration dependence, long lag time and less overall aggregation for chaotropes; whereas, kosmotropes had little or no concentration dependence, very short lag time and almost complete aggregation. Additionally, we studied the surface charge of Sup35NM to examine the stabilization or destabilization that specific ions offer the protein.