Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00106641" target="_blank" >RIV/00216224:14740/18:00106641 - isvavai.cz</a>
Výsledek na webu
<a href="http://dx.doi.org/10.1016/j.bbamem.2018.03.026" target="_blank" >http://dx.doi.org/10.1016/j.bbamem.2018.03.026</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bbamem.2018.03.026" target="_blank" >10.1016/j.bbamem.2018.03.026</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
—
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2018
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
ISSN
0005-2736
e-ISSN
—
Svazek periodika
1860
Číslo periodika v rámci svazku
9
Stát vydavatele periodika
NL - Nizozemsko
Počet stran výsledku
12
Strana od-do
1709-1720
Kód UT WoS článku
000442333600013
EID výsledku v databázi Scopus
2-s2.0-85045553236