Abstract
In vitro formation of highly ordered protein aggregates, amyloids, is influenced by the presence of ions. Here, we have studied the effect of anions on amyloid fibril formation by two different amyloidogenic proteins, human amyloid beta-42 (Aβ(42)), associated with Alzheimer disease and produced recombinantly with an N-terminal methionine (Met-Aβ(42)), and histidine-tagged NM fragment of Sup35 protein (Sup35NM-His(6)), a yeast release factor controlling protein-based inheritance, at pH values above and below their isoelectric points. We demonstrate here that pH plays a critical role in determining the effect of ions on the aggregation of Met-Aβ(42) and Sup35NM-His(6). Further, the electrophoretic mobilities of Met-Aβ(42) and Sup35NM-His(6) were measured in the presence of different anions at pH above and below the isoelectric points to understand how anions interact with these proteins when they bear a net positive or negative charge. We find that although ion-protein interactions generally follow expectations based on the anion positions within the Hofmeister series, there are qualitative differences in the aggregation behavior of Met-Aβ(42) and Sup35NM-His(6). These differences arise from a competition between nonspecific charge neutralization and screening effects and specific ion adsorption and can be explained by the different biochemical and biophysical properties of Met-Aβ(42) and Sup35NM-His(6).