Metal effects on the membrane interactions of amyloid-β peptides

Abstract

Aβ(1–42) peptide, found as aggregated species in Alzheimer’s disease brain, is linked to the onset of dementia. We detail results of 31P and 2H solid-state NMR studies of model membranes with Aβ peptides and the effect of metal ions (Cu2+ and Zn2+), which are found concentrated in amyloid plaques. The effects on the lipid bilayer and the peptide structure are different for membrane incorporated or associated peptides. Copper ions alone destabilise the lipid bilayer and induce formation of smaller vesicles, but not when Aβ(1–42) is associated with the bilayer membrane. Aβ(25–35), a fragment from the C-terminal end of Aβ(1–42), which lacks the metal coordinating sites found in the full length peptide, is neurotoxic to cortical cortex cell cultures. Addition of metal ions has little effect on membrane bilayers with Aβ(25–35) peptides. 31P magic angle spinning NMR data show that Aβ(1–42) and Aβ(1–42)-Cu2+ complexes interact at the surface of anionic phospholipid membranes. Incorporated peptides, however, appear to disrupt the membrane more severely than associated peptides. Solid-state 13C NMR was used to compare structural changes of Aβ(1–42) to those of Aβ(25–35) in model membrane systems of anionic phospholipids and cholesterol. The Aβ peptides appeared to have an increase in β-strand structure at the C-terminus when added to phospholipid liposomes. The inclusion of Cu2+ also influenced the observed chemical shift of residues from the C-terminal half, providing structural clues for the lipid-associated Aβ/metal complex. The results point to the complex pathway(s) for toxicity of the full-length peptide.

DOI: 10.1007/s00249-007-0251-2

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@article{Gehman2007MetalEO, title={Metal effects on the membrane interactions of amyloid-β peptides}, author={John D. Gehman and Caitlin C. O’Brien and Fazel Shabanpoor and John D Wade and Frances Separovic}, journal={European Biophysics Journal}, year={2007}, volume={37}, pages={333-344} }