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pubmed:abstractText |
Clusters of GM1 gangliosides act as platforms for conformational transition of monomeric, unstructured amyloid ? (A?) to its toxic ?-structured aggregates. We have previously shown that A?(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 ?-to-? conformational transition of A? on GM1 clusters, we performed spectroscopic characterization of A?(1-40) titrated with GM1. It was revealed that the thioflavin T- (ThT-) reactive ?-structure is more populated in A?(1-40) under conditions where the A?(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 A? species were not generated by smaller lyso-GM1 micelles. These findings suggest that GM1 clusters promote specific A?-A? interactions through their C-termini coupled with formation of the ThT-reactive ?-structure depending on sizes and curvatures of the clusters.
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pubmed:affiliation |
Graduate school of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
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