TY  - JOUR
AU  - Owen, Michael C.
AU  - Kulig, Waldemar
AU  - Poojari, Chetan
AU  - Rog, Tomasz
AU  - Strodel, Birgit
TI  - Physiologically-relevant levels of sphingomyelin, but not GM1, induces a β-sheet-rich structure in the amyloid-β(1-42) monomer
JO  - Biochimica et biophysica acta / Biomembranes Biomembranes [...]
VL  - 1860
IS  - 9
SN  - 0005-2736
CY  - Amsterdam
PB  - Elsevier
M1  - FZJ-2018-07752
SP  - 1709 - 1720
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29626441
UR  - <Go to ISI:>//WOS:000442333600013
DO  - DOI:10.1016/j.bbamem.2018.03.026
UR  - https://juser.fz-juelich.de/record/858916
ER  -