Interaction Site between the Protein Aggregates and Thiocyanate Ion in Aqueous Solution: A Case Study of 1-Butyl-3-methylimidazolium Thiocyanate.

To investigate the interaction site between amyloid-like protein aggregates and thiocyanate (SCN(-)) ion, we studied the relationship between protein aggregation (cytochrome c, myoglobin, lysozyme, ribonuclease A, and β-lactoglobulin) and SCN(-) ion in aqueous 1-butyl-3-methylimidazolium thiocyanate ([bmim][SCN]) solutions using optical spectroscopy. The addition of [bmim][SCN] (>10 mol % IL) to a protein solution induced protein aggregation owing to the intermolecular β-sheet structures except in the case of cytochrome c. Analysis of the content of 20 amino acid residues for each protein revealed that the degree of intermolecular β-sheet structures (β%) and midpoint concentration from the unfolding to aggregation state ([IL]1/2(U →βA)) is correlated primarily with the content of Lys residue in proteins (correlation coefficient (R(2)) = 0.97). The attractive interaction between the SCN(-) ions and NH3(+) groups of the side chain terminal of Lys residue inhibits protein aggregation owing to the intermolecular β-sheet structure. This finding might be related to the mechanism for the solubilization of amyloid aggregates by strong denaturants containing SCN(-) ions such as guanidine thiocyanate.