Manganism: the role of YPK9 protein

Several metals have toxic actions on nerve cells and neurobehavioral functioning playing a role in the genesis and development of many neurodegenerative diseases. In particular manganese(II) is a well known neurotoxic metal as it accumulates in basal ganglia inducing Manganism, a pathology with common manifestations with Parkinson's disease [1]. YPK9 gene (Yeast PARK9; also known as YOR291W) encoded protein can protect cells from manganese poisoning [2]. In fact YPK9 is a non-essential yeast gene predicted by sequence to encode a transmembrane P-type transport ATPase involved in metal coordination and transportation. Mutations in the human homolog of YPK9, ATP13A2/PARK9, have been linked to genetic forms of early onset Parkinsonism. We tested the binding ability of Mn(II) and other divalent metal ions (Cu(II), Zn(II), Ni(II)) with several peptide sequences from YPK9 with particular focus on highly conserved sequences from yeast to human. The work was carried out at different pH values and ligand/metal molar ratios by means of potentiometric and spectroscopic techniques (multidimensional and heteronuclear NMR and UV-visible), in order to evaluate and compare the coordination propensity of such fragments with Mn(II) and the other metal probes selected, with the purpose of sheding a light on the protective properties of YPK9 in Manganese-induced Parkinsonism [3-5].