Ni K-Edge XAS Suggests that Coordination of Ni II to the Unstructured Amyloidogenice Region of the Human Prion Protein Produces a Ni2 bis-u-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 Cu{sup II} coordination to the PrP. Previous work has utilized Ni{sup II} as a diamagnetic probe for Cu{sup 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{sup 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{sup II} will coordinate to PrP(93-114) by UV/Vis titrations and mass spectrometry. Ni K-edge XAS data is consistent with Ni{sup 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{sup II} centers are contained in a bis-{mu}-hydroxo dimer. We therefore suggest that Ni{sup II} may not be a suitable diamagnetic mimic for Cu{sup II} coordination within the PrP since differential coordination modes for the two metals exist.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 930292
- Report Number(s):
- BNL--80996-2008-JA
- Journal Information:
- Journal of Inorganic Biochemistry, Journal Name: Journal of Inorganic Biochemistry Journal Issue: 2 Vol. 101; ISSN JIBIDJ; ISSN 0162-0134
- Country of Publication:
- United States
- Language:
- English
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