Abstract:
In this work the structure of the Cu2+ binding site of recombinant human prion protein hPrP(23-231) was determined. For comparison PrP-derived peptides were measured in different environments.
The spectroscopic data were collected by means of EPR, ENDOR, and EXAFS spectroscopy. MD simulations were used to selected sterically possible structures.
Two clearly distinguishable peptide/Cu2+ configurations were found (species I and II) and a reliable model for the Cu2+ binding site in the octarepeat domain of PrP is presented. An equilibrium of molecules belonging to species I and II is present at several conditions. This equilibrium depends upon the Cu2+ load, pH value and buffer. The mutant form of murine PrP binds Cu2+ as species III, different of species I and II.