Spectroscopic Characterization of Intermolecular Interaction of AmyloidβPromoted on GM1 Micelles

Clusters of GM1 gangliosides act as platforms for conformational transition of monomeric, unstructured amyloidβ(Aβ) to its toxicβ-structured aggregates. We have previously shown that Aβ(1–40) accommodated on the hydrophobic/hydrophilic interface of lyso-GM1 or GM1 micelles assumesα-helical structures under ganglioside-excess conditions. For better understanding of the mechanisms underlying theα-to-βconformational transition of Aβon GM1 clusters, we performed spectroscopic characterization of Aβ(1–40) titrated with GM1. It was revealed that the thioflavin T- (ThT-) reactiveβ-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 Val39-Val40shows two distinct conformational states that are reactive with ThT, while such Aβspecies were not generated by smaller lyso-GM1 micelles. These findings suggest that GM1 clusters promote specific Aβ-Aβinteractions through their C-termini coupled with formation of the ThT-reactiveβ-structure depending on sizes and curvatures of the clusters.