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

The result's identifiers

  • Result code in 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>

  • Result on the web

    <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>

Alternative languages

  • Result language

    angličtina

  • Original language name

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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2020

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    ACS CHEMICAL NEUROSCIENCE

  • ISSN

    1948-7193

  • e-ISSN

  • Volume of the periodical

    11

  • Issue of the periodical within the volume

    4

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    27

  • Pages from-to

    535-548

  • UT code for WoS article

    000515195800005

  • EID of the result in the Scopus database

    2-s2.0-85080105414