Publication details
Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer
| Authors | |
|---|---|
| Year of publication | 2018 |
| Type | Article in Periodical |
| Magazine / Source | BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES |
| MU Faculty or unit | |
| Citation | |
| Doi | http://dx.doi.org/10.1016/j.bbamem.2018.03.026 |
| Keywords | Peptide-membrane interactions; Sphingomyelin; Lipid rafts; Amyloid-beta peptide; Molecular dynamics; Membrane simulations; GM1; Gangliosides; Peptide-ganglioside interactions |
| Description | To resolve the contribution of ceramide-containing lipids to the aggregation of the amyloid-beta protein into beta sheet rich toxic oligomers, we employed molecular dynamics simulations to study the effect of cholesterol containing bilayers comprised of POPC (70% POPC, and 30% cholesterol) and physiologically relevant concentrations of sphingomyelin (SM) (30% SM, 40% POPC, and 30% cholesterol), and the GM1 ganglioside (5% GM1, 70% POPC, and 25% cholesterol). The increased bilayer rigidity provided by SM (and to a lesser degree, GM1) reduced the interactions between the SM-enriched bilayer and the N-terminus of A beta 42 (and also residues Ser26, Asn27, and Lys28), which facilitated the formation of a beta-sheet in the normally disordered N-terminal region. A beta 42 remained anchored to the SM-enriched bilayer through hydrogen bonds with the side chain of Arg5. With beta-sheets in the at the N and C termini, the structure of A beta 42 in the sphingomyelin-enriched bilayer most resembles beta-sheet-rich structures found in higher-ordered All fibrils. Conversely, when bound to a bilayer comprised of 5% GM1, the conformation remained similar to that observed in the absence of GM1, with A beta 42 only making contact with one or two GM1 molecules. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy. |
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