The Hofmeister effect on amyloid formation using yeast prion protein

Abstract

A variety of proteins are capable of converting from their soluble forms into highly ordered fibrous cross-b aggregates (amyloids). This conversion is associated with certain pathological conditions in mammals, such as Alzheimer disease, and provides a basis for the infectious or hereditary protein isoforms (prions), causing neurodegenerative disorders in mammals and controlling heritable phenotypes in yeast. The N-proximal region of the yeast prion protein Sup35 (Sup35NM) is frequently used as a model system for amyloid conversion studies in vitro. Traditionally, amyloids are recognized by their ability to bind Congo Red dye specific to b-sheet rich structures. However, methods for quantifying amyloid fibril formation thus far were based on measurements linking Congo Red absorbance to concentration of insulin fibrils and may not be directly applicable to other amyloid-forming proteins. Here, we present a corrected formula for measuring amyloid formation of Sup35NM by Congo Red assay. By utilizing this corrected procedure, we explore the effect of different sodium salts on the lag time and maximum rate of amyloid formation by Sup35NM. We find that increased kosmotropicity promotes amyloid polymerization in accordance with the Hofmeister series. In contrast, chaotropes inhibit polymerization, with the strength of inhibition correlating with the B-viscosity coefficient of the Jones-Dole equation, an increasingly accepted measure for the quantification of the Hofmeister series.

Ion-specific Effects on Prion Nucleation and Strain Formation

“…Our data confirm an inverse Hofmeister effect on Sup35NM aggregation, which agrees with our previous work (18) and with observations for other amyloidogenic proteins that allow this conclusion while not explicitly stating it (41,42,44). An inverse Hofmeister trend arises when a colloidal particle is positively charged and hydrophilic or when a particle is negatively charged and hydrophobic (55).…”

“…These results confirm the ostensibly "inverse" Hofmeister trend previously observed (18). Having established that ion-specific effects greatly affect aggregation rate, we examined the structural and biological effects of these differing rates.…”

“…Regardless of how the conformers were induced, the ␤-sheet-rich peptides aggregate to form nuclei. Solution conditions play a great role in determining the rate of nucleation and the structure of the nucleus (17)(18)(19); however, this relationship is not yet clearly understood. After nucleation, other peptides of the same amino acid sequence are recruited to the aggregate in a unidirectional manner, analogous to "one-dimensional crystallization.…”

How ionic liquids can help to stabilize native proteins

“…For example, Yeh et al have reported evidence for Hofmeister effects of inorganic ions on amyloid formation of a yeast prion protein, 103 but there are counterexamples, where no correlations with Hofmeister rankings were found. 104 In fact, there are no convincing arguments in favour of a general Hofmeister-type behaviour of protein aggregation because conformational changes and aggregation reflect different molecular interactions.…”

Tetramers Are the Activation-competent Species of the HOCl-specific Transcription Factor HypT

“…26 and 27), thus supporting the observation of increased thermal and chemical stability of HypT upon the addition of NaCl or L-arginine. However, salt ions can also promote aggregation (29) and fibrillation of proteins such as HypF, insulin, and prion proteins (28,(33)(34)(35).…”