Interactions of Cu2+ with prion family peptide fragments: Considerations on affinity, speciation and coordination

The review describes the stability and the coordination modes of Cu2+ complexes with different regions of N-terminus prion proteins. The structural features of the different metal species are correlated both with the Cu2+-driven redox properties and with the conformational changes induced by the Cu2+ in the different metal binding regions of the protein. The formation of mixed metal complexes is also discussed.We emphasize that binding features should be discussed by referring to the species that actually forms under specific conditions (pH, buffer, etc.) rather than to the “binding site”; correlating properties with the structures of the so called ‘binding sites’ may lead to misinterpretation of the experimental results, since a ‘binding site’ often corresponds to a mixture of species. We also highlight that ignoring species that form with ligands other than the prion peptide (e.g. the buffer) may lead to underestimating their role in crucial processes (e.g. redox activity).

► Stability constants of Cu2+ complexes with different regions of PrP N-terminus.
► Structures of the copper centres are crucial to fully understand PrP functions.
► Importance of a multi-technique (i.e. potentiometric and spectroscopic) approach.
► Speciation: a way to solve conflicting conclusions on metal-PrP redox activity.