Interaction of selected divalent metal ions with human ataxin-3 Q36

The mode of interaction of ataxin-3 Q36 (AT-3 Q36) with selected endogenous and exogenous metal ions, namely, Zn²⁺, Cu²⁺, Ni²⁺, and Cd²⁺, was examined. Metal-ion-induced structural changes of the protein were monitored by fluorescence as well as Fourier transform Raman spectroscopy. We found that the cations tested lead to a decrease in α-helical content and a concurrent increase in β-sheet as well as undefined (β-turn and random-coil) structures. The most evident effect was observed for copper and nickel cations. After titration with these cations, the AT3 Q36 secondary structure content (27% α-helices in the presence of either ion, 31 and 27% β-sheets for Cu²⁺ and Ni²⁺, respectively) was similar to that observed for the aggregated form of the protein (27% α-helices, 36% β-sheets). Using the 1-anilinonaphthalene-8-sulfonate hydrophobic fluorescence probe, we showed that the presence of the metal ions tested led to the formation of solvent-exposed hydrophobic patches of AT-3 Q36, and that such an effect decreased with increasing ionic radius.