Metal-dependent α-helix formation promoted by the glycine-rich octapeptide region of prion protein

Prion diseases share a common feature in that the normal cellular prion protein (PrP(C)) converts to a protease-resistant isoform PrP(C). The α-helix-rich C-terminal half of PrP(C) is partly converted into β-sheet in PrP(Sc). We have examined by Raman spectroscopy the structure of an octapeptide PHGGGWGQ that appears in the N-terminal region of PrP(C) and a longer peptide containing the octapeptide region. The peptides do not assume any regular structure without divalent metal ions, whereas Cu(II) binding to the HGGG segment induces formation of α-helical structure on the C-terminal side of the peptide chain. The N-terminal octapeptide of prion protein may be a novel structural motif that acts as a promoter of α-helix formation.