NR AYDF
AU Pushie,M.J.; Ross,A.R.; Vogel,H.J.
TI Mass spectrometric determination of the coordination geometry of potential copper(II) surrogates for the mammalian prion protein octarepeat region
QU Analytical Chemistry 2007 Aug 1; 79(15): 5659-67
PT journal article; research support, non-u.s. gov't
AB The N-terminal domain of mammalian prion proteins contains several tandem repeats of the octapeptide PHGGGWGQ, each one capable of selectively binding up to 1 equiv of Cu2+. Under saturating conditions Cu2+ is known to coordinate the HGG portion of the repeat sequence via the histidine imidazole side chain, two deprotonated amide N-atoms, and a backbone carbonyl O-atom. Using appropriate selection criteria, we have generated a short list of candidate metal ions (Co3+, Ni2+, Pd2+, Pt2+) that can serve as potential surrogates for Cu2+. The selected metal ions were screened for binding interactions with the OR-derived peptide fragment AcHGGGWNH2 (Ac = acetyl, amino acid residues in italics) using electrospray ionization mass spectrometry. The coordination geometries of these metal ions with the synthetic OR peptide were subsequently determined from fragment analysis using collision-induced dissociation tandem mass spectrometry. Our results indicate that, although Co3+, Pd2+, and Pt2+ all bind to the OR fragment via the peptide backbone to varying extents, each of these metal ions appears to associate with the peptide in a unique manner, which is distinct from the way in which Cu2+ is coordinated. This work illustrates the extremely strong selectivity for Cu2+ of this highly conserved region of the mammalian prion protein.
MH Amino Acid Sequence; Binding Sites; Cations, Divalent; Cobalt/analysis/chemistry/metabolism; Copper/chemistry/*metabolism; Histidine/chemistry; Imidazoles/chemistry; Molecular Sequence Data; Nickel/analysis/chemistry/metabolism; Palladium/analysis/chemistry/metabolism; Platinum/analysis/chemistry/metabolism; Prions/analysis/*chemistry/metabolism; Protein Conformation; Spectrometry, Mass, Electrospray Ionization/*methods
AD Structural Biology Research Group, Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta, T2N 1N4, Canada.
SP englisch
PO USA