COPPER-BINDING TO THE N-TERMINAL TANDEM REPEAT REGIONS OF MAMMALIAN AND AVIAN PRION PROTEIN

Mammalian prion protein (PrP) is a normal cellular protein (PrPc) whic h through post-translational modification produces the infectious prio n protein (PrPsc). We have shown, using mass spectrometry, that synthe tic peptides containing three or four copies of an octapeptide repeat sequence (PHGGGWGQ), found in a highly conserved N-terminal domain of PrP, preferentially bind copper over other metals. Peptides from the a nalogous region of chicken PrP, which contains an N-terminal repeat do main of the hexapeptide (NPGYPH), showed similar specificity for coppe r binding. In addition, gel filtration chromatography demonstrated con centration dependent binding of copper to the mammalian tetra repeat P rP peptide. These results suggest that PrP may be a copper binding pro tein in vivo. (C) 1995 Academic Press, Inc.