One octarepeate expansion to the human prion protein alters both the Zn2+ and Cu2+ coordination environments within the octarepeate domain.
The influence of a single octarepeat expansion on the Cu(II) and Zn(II) coordination environments within the octarepeat domain of the human prion protein is examined. Using X-ray absorption spectroscopy and diethyl pyrocarbonate labeling studies, we find that at low copper concentrations the "normal" octarepeat domain (four PHGGGWGQ repeats) coordinates Zn(II) in an (N/O)(6) coordination environment with two histidine residues and Cu(II) in a redox-inactive (N/O)(4) coordination environment using one imidazole residue. Expansion of the octarepeat region by one repeat (five PHGGGWGQ repeats) yields a three-histidine (N/O)(6) coordination environment for Zn(II) and a two-histidine (N/O)(4) coordination environment for Cu(II) at low copper concentrations. This Cu(II)[(N/O)(2)-histidine(2)] coordination motif is redox-active and capable of generating H(2)O(2) under reducing aerobic conditions.
Department of Chemistry/216, University of Nevada, Reno, Reno, Nevada 89557, United States. shearer@unr.edu
Jason
J
Shearer
Kyle E
KE
Rosenkoetter
Paige E
PE
Callan
Chi
C
Pham
D020134:Catalytic Domain; D002413:Cations, Divalent; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004047:Diethyl Pyrocarbonate / Q000737:chemistry; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D056928:X-Ray Absorption Spectroscopy; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
D002413:Cations, Divalent; D010446:Peptide Fragments; D011328:Prions; C541448:prion protein (76-114), human; D006639:Histidine; D003300:Copper; D006861:Hydrogen Peroxide; D015032:Zinc; D004047:Diethyl Pyrocarbonate
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