The Interaction of Aβ(1-40) Peptide with Lipid Bilayers and Ganglioside As Studied by Multinuclear Solid-State NMR

摘要

Amyloid β-peptide (Aβ) is a major component of plaques in Alzheimer's disease, and formation of senile plaques has been suggested to originate from regions of neuronal membrane rich in gangliosides. We have analyzed the interaction of Aβ with lipid bilayers by multinuclear NMR using ~(15)N, ~(31)P and ~(13)C nuclei. The result of the present study implies that the fibrillogenic seed nucleus involves an interaction of His residues with the sialic acid moiety of GM1. Moreover, Aβ(1-40) with ganglioside GM1 perturbs the bilayer structure to form a non-lamellar structure such as hexagonal H_(11) lipids and also produces single vesicles or micelles, as shown by angular-dependent ~(31)P NMR experiments. In conclusion, the Aβ peptide penetrates into the lipid bilayer, takes on an α-helical form, and produces non-lamellar lipid and micelles.