Copper ions reportedly bind to the cellular prion (PrPC) and induce PrP proteinase K (PK) resistant from (PrPres). PrPC also plays a role in response to oxidative stress. By using purified human PrP23-98 containing octarepeats, we have found that Cu(II) induces PrPres determined by Western blots and atomic force microscopy, and structural changes detected by hydrogen/deuterium exchange in the PrP N-terminus. Therefore, we have provided the evidence that copper ions play an important role in the change of N-terminus of human prion protein. (C) 2018 Published by Elsevier Inc.