Journal Article

FZJ-2018-07752

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Physiologically-relevant levels of sphingomyelin, but not GM1, induces a β-sheet-rich structure in the amyloid-β(1-42) monomer

Owen, M. C. ; Kulig, W. ; Poojari, C. ; Rog, T. ; Strodel, B. (Corresponding author)FZJ*

2018
Elsevier Amsterdam

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Please use a persistent id in citations: doi:10.1016/j.bbamem.2018.03.026

Abstract: To resolve the contribution of ceramide-containing lipids to the aggregation of the amyloid-β protein into β-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 Aβ42 (and also residues Ser26, Asn27, and Lys28), which facilitated the formation of a β-sheet in the normally disordered N-terminal region. Aβ42 remained anchored to the SM-enriched bilayer through hydrogen bonds with the side chain of Arg5. With β-sheets in the at the N and C termini, the structure of Aβ42 in the sphingomyelin-enriched bilayer most resembles β-sheet-rich structures found in higher-ordered Aβ fibrils. Conversely, when bound to a bilayer comprised of 5% GM1, the conformation remained similar to that observed in the absence of GM1, with Aβ42 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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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 551 - Functional Macromolecules and Complexes (POF3-551) (POF3-551)

Appears in the scientific report 2018

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Database coverage:
BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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