Amyloid-beta–copper interaction studied by simultaneous nitrogen K and copper L2,3-edge soft X-ray absorption spectroscopy

Abstract

HighlightsAmyloid-beta-copper interaction leads to distinct X-ray spectroscopic signatures After interaction monovalent copper(I) is foundThe X-ray signatures strongly depend on the pH and incubation conditions

Copper trafficking systems in cells: insights into coordination chemistry and toxicity

“…218 In accordance with previous studies, 215,216 the pre-peak feature in the N K-edge spectra of Aβ at 399.3 eV disappears upon treatment with Cu(II), possibly attributed to the ligation of the N-terminal primary amine and His residues. 218 At the same time, new peaks at 928.5 eV and 932.5 eV appear, the former of which is presumed to be due to the excitation of d 9 Cu(II) complexes. The strong dipole allowing 2p → 3p absorption is usually suppressed in the case of closed-shell d 10 Cu(I), but the coordination of Aβ may allow the hybridization of the Cu 3d orbitals with Cu 4sp and the ligand orbitals to exhibit a new peak at 932.5 eV.…”

“…215 It should be noted that it is challenging to simultaneously investigate a metal center and its ligand environment using hard X-rays because of the absence of N resonant excitation. 218,219 Luo, Dreiser, and coworkers recently employed XAS in the soft X-ray range, which allows for studying Cu L 2,3 -edges and the nitrogen K-edge of Cu(I/II)-Aβ complexes under exactly the same conditions as those in the original sample. 218 In accordance with previous studies, 215,216 the pre-peak feature in the N K-edge spectra of Aβ at 399.3 eV disappears upon treatment with Cu(II), possibly attributed to the ligation of the N-terminal primary amine and His residues.…”

“…218,219 Luo, Dreiser, and coworkers recently employed XAS in the soft X-ray range, which allows for studying Cu L 2,3 -edges and the nitrogen K-edge of Cu(I/II)-Aβ complexes under exactly the same conditions as those in the original sample. 218 In accordance with previous studies, 215,216 the pre-peak feature in the N K-edge spectra of Aβ at 399.3 eV disappears upon treatment with Cu(II), possibly attributed to the ligation of the N-terminal primary amine and His residues. 218 At the same time, new peaks at 928.5 eV and 932.5 eV appear, the former of which is presumed to be due to the excitation of d 9 Cu(II) complexes.…”

“…Quantification of Cu(I) and Cu (II) is limited due to the smaller amounts of 3d holes in Cu(I); however, this observation still suggests the redox cycling behavior of Cu(I/II)-Aβ via bis-His coordination. 218 Cu(I/II)-Aβ could produce ROS through Fenton-like reactions under aerobic conditions, which induce oxidative damage in biomolecules (vide supra; Fig. 4).…”

Cross interactions between Apolipoprotein E and amyloid proteins in neurodegenerative diseases

“…ApoE is one of many proteins that can interact with Aβ, and the interaction of ApoE with Aβ can affect various stages of Aβ homeostasis as discussed below. However, the binding strength/affinity of ApoE/Aβ complexes varies depending on many factors such as the isoforms, lipidation state, oxidation and concentration of ApoE, as well as the length, concentration, morphology and source (native or synthetic) of Aβ, in addition to the local environmental conditions like receptor concentrations, chaperone concentration, metal ions and electrolyte concentration, pH, temperature, molecular crowding, inflammasome, and other factors that can affect proteostasis [47] , [48] , [49] . For instance, recombinant ApoE2, E3 and E4 preferably bind to Aβ peptides containing more β-sheet structures with a binding affinity of 20 nM in vitro [50] , and lipid-free ApoE binds stronger to immobilized Aβ than lipidated ApoE does [51] .…”