Interaction of Cu(II) and Ni(II) with Ypk9 protein fragment via NMR studies.
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 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.
Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
Massimiliano Francesco
MF
Peana
Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
Serenella
S
Medici
Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
Alessia
A
Ledda
Department of Chemical and Geological Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy.
Valeria Marina
VM
Nurchi
Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
Maria Antonietta
MA
Zoroddu
D000595:Amino Acid Sequence; D002412:Cations; D003300:Copper / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D006180:Proton-Translocating ATPases / Q000737:chemistry*
D002412:Cations; D010446:Peptide Fragments; D003300:Copper; D009532:Nickel; D006180:Proton-Translocating ATPases