The mode of interaction of ataxin-3 Q36 (AT-3 Q36) with selected endogenous and exogenous metal ions, namely, , , , and , 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 -helical content and a concurrent increase in -sheet as well as undefined (-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% -helices in the presence of either ion, 31 and 27% -sheets for and , respectively) was similar to that observed for the aggregated form of the protein (27% -helices, 36% -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.