NR AWUS
AU Shearer,J.; Soh,P.
TI Ni K-edge XAS suggests that coordination of Ni(II) to the unstructured amyloidogenic region of the human prion protein produces a Ni(2) bis-mu-hydroxo dimer
QU Journal of Inorganic Biochemistry 2007 Feb; 101(2): 370-3
PT in vitro; journal article; research support, non-u.s. gov't; research support, u.s. gov't, non-p.h.s.
AB Prion diseases are thought to be caused by the misfolding of the ubiquitous neuronal membrane prion protein (PrP) through an unknown mechanism that may involve Cu(II) coordination to the PrP. Previous work has utilized Ni(II) as a diamagnetic probe for Cu(II) coordination [C.E. Jones, M. Klewpatinond, S.R. Abdelraheim, D.R. Brown, J.H. Viles, J. Mol. Biol. 346 (2005) 1393-1407]. Herein we investigate Ni(II) coordination to the PrP fragment PrP(93-114) (AcN-GGTHSQWNKPSKPKTNMKHMAG) at pH=10.0 by Ni K-edge X-ray absorption spectroscopy (XAS). We find that two equivalents of Ni(II) will coordinate to PrP(93-114) by UV/Vis titrations and mass spectrometry. Ni K-edge XAS data is consistent with Ni(II) ligated by five N/O based ligands (three N/O ligands at 2.01(2) Angstrom and two at 1.855(2) Angstrom). We were also able to locate a Ni-Ni vector at 3.1(1) Angstrom, which suggests the two Ni(II) centers are contained in a bis-mu-hydroxo dimer. We therefore suggest that Ni(II) may not be a suitable diamagnetic mimic for Cu(II) coordination within the PrP since differential coordination modes for the two metals exist.
MH Amino Acid Sequence; Amyloid/chemistry/genetics; Copper/chemistry; Humans; Magnetics; Molecular Probes; Molecular Sequence Data; Nickel/*chemistry; Peptide Fragments/chemistry/genetics; Prions/*chemistry/genetics; Protein Folding; Spectrum Analysis; X-Rays
AD Department of Chemistry/216, University of Nevada, Reno, NV 89557, USA. shearer@chem.unr.edu
SP englisch
PO USA