NGUYEN, Phuong.Hoang; CAMPANERA, Josep Maria; NGO, Son Tung; LOQUET, Antoine; DERREUMAUX, Philippe

doi:10.1021/acs.jpcb.9b05288

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NGUYEN, Phuong.Hoang

CAMPANERA, Josep Maria

NGO, Son Tung

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Ce document a été publié dans

Journal of the Chemical Society B: Physical Organic Journal of the Chemical Society B: Physical Organic. 2019, vol. 123, n° 17, p. 3643-3648

Résumé en anglais

Alzheimer’s disease (AD) is characterized by the accumulation of extracellular Aβ42 and Aβ40 oligomers and plaques. In a recent computational study, we found that the presence of the residues I41 and A42 increases significantly the propensity of Aβ to form a tetrameric β-barrel structure in a bilayer mimicking a neuronal membrane. In this work, we have determined the propensity of the two Aβ proteins to form tetrameric β-barrel structures in aqueous solution using four atomistic protein fields, that is Amber99SB-ILDN/TIP3P, OPLS/TIP3P, CHARMM36m/TIP3P-modified and Amber99SB/DISP. Extensive replica exchange molecular dynamics simulations make it clear that a β-barrel, made of two distinct β-hairpin motifs and an asymmetric arrangement of eight anti-parallel β-strands with an inner pore diameter of 0.7 nm, exists transiently for Aβ42 peptide, but this is less the case for Aβ40 peptide, due to the change of the CHC-CHC and the Cter-Cter interfaces. This study has several implications in AD.< Réduire

URI

https://oskar-bordeaux.fr/handle/20.500.12278/3808

DOI

http://dx.doi.org/10.1021/acs.jpcb.9b05288

Project ANR

Dynamique des membranes transductrices d'énergie : biogénèse et organisation supramoléculaire. - ANR-11-LABX-0011
Centre d'analyse de systèmes complexes dans les environnements complexes - 11-EQPX-0008

Unités de recherche

CBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248