Structural Insight into Redox Dynamics of Copper Bound N-Truncated Amyloid-β Peptides from in Situ X-ray Absorption Spectroscopy

Inorganic Chemistry
Victor A StreltsovStephen P Best

Abstract

X-ray absorption spectroscopy of CuII amyloid-β peptide (Aβ) under in situ electrochemical control (XAS-EC) has allowed elucidation of the redox properties of CuII bound to truncated peptide forms. The Cu binding environment is significantly different for the Aβ1-16 and the N-truncated Aβ4-9, Aβ4-12, and Aβ4-16 (Aβ4-9/12/16) peptides, where the N-truncated sequence (F4R5H6) provides the high-affinity amino-terminal copper nickel (ATCUN) binding motif. Low temperature (ca. 10 K) XAS measurements show the adoption of identical CuII ATCUN-type binding sites (CuIIATCUN) by the first three amino acids (FRH) and a longer-range interaction modeled as an oxygen donor ligand, most likely water, to give a tetragonal pyramid geometry in the Aβ4-9/12/16 peptides not previously reported. Both XAS-EC and EPR measurements show that CuII:Aβ4-16 can be reduced at mildly reducing potentials, similar to that of CuII:Aβ1-16. Reduction of peptides lacking the H13H14 residues, CuII:Aβ4-9/12, require far more forcing conditions, with metallic copper the only metal-based reduction product. The observations suggest that reduction of CuIIATCUN species at mild potentials is possible, although the rate of reduction is significantly enhanced by involvement...Continue Reading

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Citations

Nov 30, 2018·Metallomics : Integrated Biometal Science·Ewelina StefaniakWojciech Bal
Jul 4, 2019·Metallomics : Integrated Biometal Science·Francesco StellatoSilvia Morante

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