MANGANISM: THE ROLE OF YPK9 PROTEIN

MANGANISM: THE ROLE OF YPK9 PROTEIN
MARIA ANTONIETTA ZORODDU (1), MASSIMILIANO PEANA (1), SERENELLA MEDICI (1),
MAURIZIO REMELLI (2)
(1): Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, Sassari, 07100, Italy
(2): Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Via L. Borsari 16, Ferrara,
I-44100 Italy;
ABSTRACT
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].
Figure 1 – The connection between genetic and environmental PD causes in a graphical interpretation for the
Front Cover of the Dalton Transaction, Issue 17 (2013) [6].
Acknowledgements
This work was supported by Regione Autonoma Sardegna L.R.7/2007, “Promozione della ricerca scientifica e
dell’innovazione tecnologica in Sardegna” program, project CRP 26712 “Nanopolveri e nanoparticelle
metalliche: il vero responsabile della sindrome di Quirra?”.
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