The rich chemistry of the copper and zinc sites in cellular prion protein

Abstract

Research over the last decade clearly demonstrates that the function of the cellular form of the prion protein, PrP C, is related to its ability to bind copper and zinc. Zinc (Zn 2+) coordination is homogeneous and localized to the octarepeat domain, with participation of the histidine side chains. In contrast, copper uptake is complex and dependent on the oxidation state of the metal ion (Cu + or Cu 2+), and its concentration. This chapter will cover a brief history of PrP C -metal interactions leading to the current structural models, a recently recognized relationship between Cu 2+ coordination and inherited prion disease arising from octarepeat inserts, and new findings that suggest an electrochemical basis for PrP C neuroprotection and transmembrane signaling.