Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer

Original language 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ISSN

0005-2736

e-ISSN

—

Volume of the periodical

1860

Issue of the periodical within the volume

9

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

12

Pages from-to

1709-1720

UT code for WoS article

000442333600013

EID of the result in the Scopus database

2-s2.0-85045553236