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

FATAFTA, H., C. POOJARI, A. SAYYED-AHMAD, B. STRODEL and Michael Christopher OWEN. Role of Oxidized Gly25, Gly29, and Gly33 Residues on the Interactions of A beta(1-42) with Lipid Membranes. ACS CHEMICAL NEUROSCIENCE. WASHINGTON: AMER CHEMICAL SOC, 2020, vol. 11, No 4, p. 535-548, 27 pp. ISSN 1948-7193. Available from: https://dx.doi.org/10.1021/acschemneuro.9b00558.

Basic information

• Original name: Role of Oxidized Gly25, Gly29, and Gly33 Residues on the Interactions of A beta(1-42) with Lipid Membranes
• Authors: FATAFTA, H., C. POOJARI, A. SAYYED-AHMAD, B. STRODEL and Michael Christopher OWEN (124 Canada, guarantor, belonging to the institution).
• Edition: ACS CHEMICAL NEUROSCIENCE, WASHINGTON, AMER CHEMICAL SOC, 2020, 1948-7193.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 4.418
• RIV identification code: RIV/00216224:14740/20:00118347
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1021/acschemneuro.9b00558
• UT WoS: 000515195800005
• Keywords in English: Amyloid-beta peptide; molecular dynamics; membrane simulations; oxidative stress; GM1; peptide membrane interactions
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

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.