title: 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 amyloid β (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 α-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)-Val(40) 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.
authors.affiliation: Graduate school of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Yagi-Utsumi
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuo
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanagisawa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Gekko
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato