Role of Oxidized Gly25, Gly29, and Gly33 Residues on the Interactions of A beta(1-42) with Lipid Membranes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00118347" target="_blank" >RIV/00216224:14740/20:00118347 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acschemneuro.9b00558" target="_blank" >https://pubs.acs.org/doi/10.1021/acschemneuro.9b00558</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acschemneuro.9b00558" target="_blank" >10.1021/acschemneuro.9b00558</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Role of Oxidized Gly25, Gly29, and Gly33 Residues on the Interactions of A beta(1-42) with Lipid Membranes

Popis výsledku v původním jazyce

Oxidative stress is known to play an important role in the pathogenesis of Alzheimer's disease. Moreover, it is becoming increasingly evident that the plasma membrane of neurons plays a role in modulating the aggregation and toxicity of Alzheimer's amyloid-beta peptide (A beta). In this study, the combined and interdependent effects of oxidation and membrane interactions on the 42 residues long A beta isoform are investigated using molecular simulations. Hamiltonian replica exchange molecular dynamics simulations are utilized to elucidate the impact of selected oxidized glycine residues of A beta 42 on the interactions of the peptide with a model membrane comprised of 70% POPC, 25% cholesterol, and 5% of the ganglioside GM1. The main findings are that, independent of the oxidation state, A beta prefers binding to GM1 over POPC, which is further enhanced by the oxidation of Gly29 and Gly33 and reduced the formation of beta-sheet. Our results suggest that the differences observed in A beta 42 conformations and its interaction with a lipid bilayer upon oxidation originate from the position of the oxidized Gly residue with respect to the hydrophobic sequence of A beta 42 involving the Gly29-XXX-Gly33-XXX-Gly37 motif and from specific interactions between the peptide and the terminal sugar groups of GM1.

Název v anglickém jazyce

Role of Oxidized Gly25, Gly29, and Gly33 Residues on the Interactions of A beta(1-42) with Lipid Membranes

Popis výsledku anglicky

Oxidative stress is known to play an important role in the pathogenesis of Alzheimer's disease. Moreover, it is becoming increasingly evident that the plasma membrane of neurons plays a role in modulating the aggregation and toxicity of Alzheimer's amyloid-beta peptide (A beta). In this study, the combined and interdependent effects of oxidation and membrane interactions on the 42 residues long A beta isoform are investigated using molecular simulations. Hamiltonian replica exchange molecular dynamics simulations are utilized to elucidate the impact of selected oxidized glycine residues of A beta 42 on the interactions of the peptide with a model membrane comprised of 70% POPC, 25% cholesterol, and 5% of the ganglioside GM1. The main findings are that, independent of the oxidation state, A beta prefers binding to GM1 over POPC, which is further enhanced by the oxidation of Gly29 and Gly33 and reduced the formation of beta-sheet. Our results suggest that the differences observed in A beta 42 conformations and its interaction with a lipid bilayer upon oxidation originate from the position of the oxidized Gly residue with respect to the hydrophobic sequence of A beta 42 involving the Gly29-XXX-Gly33-XXX-Gly37 motif and from specific interactions between the peptide and the terminal sugar groups of GM1.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

ACS CHEMICAL NEUROSCIENCE

ISSN

1948-7193

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

27

Strana od-do

535-548

Kód UT WoS článku

000515195800005

EID výsledku v databázi Scopus

2-s2.0-85080105414