Spectroscopic characterization of intermolecular interaction of amyloid β promoted on GM1 micelles

Abstract

Clusters of GM1 gangliosides act as platforms for conformational transition of monomeric, unstructured β amyloid (Aβ) to its toxic β-structured aggregates. We have previously shown that Aβ (1-40) accommodated on the hydrophobic/hydrophilic interface of lyso-GM1 or GM1 micelles assumes -helical structures under ganglioside-excess conditions. For better understanding of the mechanisms underlying the α-to-β conformational transition of Aβ on GM1 clusters, we performed spectroscopic characterization of Aβ(1-40) titrated with GM1. It was revealed that the thioflavin T- (ThT-) reactive β-structure is more populated in Aβ(1-40) under conditions where the Aβ(1-40) density on GM1 micelles is high. Under this circumstance, the C-terminal hydrophobic anchor Val 39-Val40 shows two distinct conformational states that are reactive with ThT, while such Aβ species were not generated by smaller lyso-GM1 micelles. These findings suggest that GM1 clusters promote specific Aβ-Aβ interactions through their C-termini coupled with formation of the ThT-reactive β-structure depending on sizes and curvatures of the clusters. Copyright 2011 Maho Yagi-Utsumi et al.