Varied Probability of Staying Collapsed/Extended at the Conformational Equilibrium of Monomeric Aβ40 and Aβ42.

Abstract : In present study, we set out to investigate the conformation dynamics of Aβ40 and Aβ42 through exploring the impact of intra-molecular interactions on conformation dynamics using equilibrium molecular dynamics simulations. Our 40 microsecond-scale simulations reveal heterogeneous conformation ensembles of Aβ40 and Aβ42 that encompass ~35% β-strand and ~60% unstructured coils. Two conformational states were identified in both alloforms: a collapsed state (CS) that resembles the structural motif of face-to-face hydrophobic clustering in amyloid fibrils, and an extended state (ES) that features the structural characteristics of anti-parallel β-sheets in amyloid oligomers. In Aβ40, the C-terminus remains unstructured and rarely interacts with other parts, thereof the hydrophobic clustering is in loose contact and the peptide assumes ES with high probability. In contrast, the C-terminus of Aβ42 adopts a β-strand structure that strongly interacts with segments E3-R5 and V18-A21. The active association leads to a more compact hydrophobic collapse and refrain the alloform from ES. Based on the structural characterization, we propose that the fibril and oligomer assembly pathways could respectively take off from CS and ES, and their aggregation propensity may be governed by the probability of visiting the corresponding conformational states at the equilibrium.
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Article dans une revue
Scientific Reports, Nature Publishing Group, 2015, 5, pp.11024
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http://hal.univ-grenoble-alpes.fr/hal-01199233
Contributeur : Frank Thomas <>
Soumis le : mardi 15 septembre 2015 - 10:29:14
Dernière modification le : lundi 19 février 2018 - 14:34:03

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  • HAL Id : hal-01199233, version 1
  • PUBMED : 26046578

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Wanling Song, Yuanyuan Wang, Jacques-Philippe Colletier, Huaiyu Yang, Yechun Xu. Varied Probability of Staying Collapsed/Extended at the Conformational Equilibrium of Monomeric Aβ40 and Aβ42.. Scientific Reports, Nature Publishing Group, 2015, 5, pp.11024. 〈hal-01199233〉

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