Abstract
Most proteins implicated in neurodegenerative diseases bind metal ions, notably copper and zinc. Metal ion binding may be part of the protein's function or, alternatively, may promote a deleterious gain of function. With regard to Cu(2+) ions, electron paramagnetic resonance techniques have proven to be instrumental in determining the biophysical characteristics of the copper binding sites, as well as structural features of the coordinating protein and how they are impacted by metal binding. Here, the most useful methods are described as they apply to the prion protein, which serves as a model for the broader spectrum of neurodegenerative proteins.