Spectroscopic aspects of metal ions interaction with a multi-histidinic peptide fragment

Multihistidinic proteins are involved in different neurodegenerative pathologies such as Parkinson’s, Alzheimer’s and prion diseases. Their role in the genesis and development of such pathologies is being slowly unveiled, and seems to be connected to protein interaction with metal ions, especially the divalent ones. Proteins involved in these diseases are very different in nature and function, but they all have a common feature: the presence of several histidine residues in their sequences. Histidines are well known for being an effective anchoring site for metal ions, and their binding to the metal centre often results also in the coordination of neighbouring residues and a change in the structural conformation of the protein. We have used a multihistidinic domain in Cap43 protein as a model for the study of divalent cations behaviour, such as Ni(II), Cu(II), Zn(II), Co(II) and Mn(II), towards protein coordination. The study was carried out at different metal-to-peptide molar ratios and pH values through a series of potentiometric and spectroscopic experiments (mono- and bi-dimensional multinuclear NMR, EPR, UV-Vis). Data collected have been used to calculate a model for the metal-peptide complex, evidencing an interesting behaviour for each metal tested. Here we would like to report our results.