Ni K-edge XAS suggests that coordination of NiII to the unstructured amyloidogenic region of the human prion protein produces a Ni2 bis-μ-hydroxo dimer

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 CuII coordination to the PrP. Previous work has utilized NiII as a diamagnetic probe for CuII 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 NiII 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 NiII will coordinate to PrP(93–114) by UV/Vis titrations and mass spectrometry. Ni K-edge XAS data is consistent with NiII ligated by five N/O based ligands (three N/O ligands at 2.01(2) Å and two at 1.855(2) Å). We were also able to locate a Ni–Ni vector at 3.1(1) Å, which suggests the two NiII centers are contained in a bis-μ-hydroxo dimer. We therefore suggest that NiII may not be a suitable diamagnetic mimic for CuII coordination within the PrP since differential coordination modes for the two metals exist.