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Interaction of Cu(II) and Ni(II) with Ypk9 protein fragment via NMR studies.


ABSTRACT: P?D?E?K?H?E?L? (PK9-H), a fragment of Ypk9, the yeast homologue of the human Park9 protein, was studied for its coordination abilities towards Ni(II) and Cu(II) ions through mono- and bi-dimensional NMR techniques. Both proteins are involved in the transportation of metal ions, including manganese and nickel, from the cytosol to the lysosomal lumen. Ypk9 showed manganese detoxification role, preventing a Mn-induced Parkinsonism (PD) besides mutations in Park9, linked to a juvenile form of the disease. Here, we tested PK9-H with Cu(II) and Ni(II) ions, the former because it is an essential element ubiquitous in the human body, so its trafficking should be strictly regulated and one cannot exclude that Ypk9 may play a role in it, and the latter because, besides being a toxic element for many organisms and involved in different pathologies and inflammation states, it seems that the protein confers protection against it. NMR experiments showed that both cations can bind PK9-H in an effective way, leading to complexes whose coordination mode depends on the pH of the solution. NMR data have been used to build a model for the structure of the major Cu(II) and Ni(II) complexes. Structural changes in the conformation of the peptide with organized side chain orientation promoted by nickel coordination were detected.

SUBMITTER: Peana MF 

PROVIDER: S-EPMC3982466 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Interaction of Cu(II) and Ni(II) with Ypk9 protein fragment via NMR studies.

Peana Massimiliano Francesco MF   Medici Serenella S   Ledda Alessia A   Nurchi Valeria Marina VM   Zoroddu Maria Antonietta MA  

TheScientificWorldJournal 20140324


P₁D₂E₃K₄H₅E₆L₇ (PK9-H), a fragment of Ypk9, the yeast homologue of the human Park9 protein, was studied for its coordination abilities towards Ni(II) and Cu(II) ions through mono- and bi-dimensional NMR techniques. Both proteins are involved in the transportation of metal ions, including manganese and nickel, from the cytosol to the lysosomal lumen. Ypk9 showed manganese detoxification role, preventing a Mn-induced Parkinsonism (PD) besides mutations in Park9, linked to a juvenile form of the di  ...[more]

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