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

J 2018

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

OWEN, Michael Christopher, W. KULIG, C. POOJARI, T. ROG, B. STRODEL et. al.

Basic information

Original name

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

Authors

OWEN, Michael Christopher (124 Canada, guarantor, belonging to the institution), W. KULIG (246 Finland), C. POOJARI (246 Finland), T. ROG (246 Finland) and B. STRODEL (276 Germany)

Edition

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, AMSTERDAM, ELSEVIER SCIENCE BV, 2018, 0005-2736

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.790

RIV identification code

RIV/00216224:14740/18:00106641

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.bbamem.2018.03.026

UT WoS

000442333600013

Keywords in English

Peptide-membrane interactions; Sphingomyelin; Lipid rafts; Amyloid-beta peptide; Molecular dynamics; Membrane simulations; GM1; Gangliosides; Peptide-ganglioside interactions

Abstract

V originále

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.

Links

6SA18009, interní kód MU

Name: The Protective Role of Gangliosides in Lipid-Mediated Amyloid-beta oligomerization in Alzheimer's disease (Acronym: Alzheimer's Lipids)

Investor: South-Moravian Region, Incoming grants

Citovat

OWEN, Michael Christopher, W. KULIG, C. POOJARI, T. ROG and B. STRODEL. Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES. AMSTERDAM: ELSEVIER SCIENCE BV, 2018, vol. 1860, No 9, p. 1709-1720. ISSN 0005-2736. Available from: https://dx.doi.org/10.1016/j.bbamem.2018.03.026.

@article{1506977,
   author = {Owen, Michael Christopher and Kulig, W. and Poojari, C. and Rog, T. and Strodel, B.},
   article_location = {AMSTERDAM},
   article_number = {9},
   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},
   language = {eng},
   issn = {0005-2736},
   journal = {BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES},
   title = {Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer},
   volume = {1860},
   year = {2018}
}

TY  - JOUR
ID  - 1506977
AU  - Owen, Michael Christopher - Kulig, W. - Poojari, C. - Rog, T. - Strodel, B.
PY  - 2018
TI  - Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer
JF  - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
VL  - 1860
IS  - 9
SP  - 1709-1720
EP  - 1709-1720
PB  - ELSEVIER SCIENCE BV
SN  - 00052736
KW  - Peptide-membrane interactions
KW  - Sphingomyelin
KW  - Lipid rafts
KW  - Amyloid-beta peptide
KW  - Molecular dynamics
KW  - Membrane simulations
KW  - GM1
KW  - Gangliosides
KW  - Peptide-ganglioside interactions
N2  - 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.
ER  -

OWEN, Michael Christopher, W. KULIG, C. POOJARI, T. ROG and B. STRODEL. Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer. \textit{BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES}. AMSTERDAM: ELSEVIER SCIENCE BV, 2018, vol.~1860, No~9, p.~1709-1720. ISSN~0005-2736. Available from: https://dx.doi.org/10.1016/j.bbamem.2018.03.026.

Detailed Information on Publication Record