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Schledorn M, Meier BH, Böckmann A. Alternative salt bridge formation in Aβ-a hallmark of early-onset Alzheimer's disease?. Front Mol Biosci. 2015;2:14doi: 10.3389/fmolb.2015.00014.
Schledorn, M., Meier, B. H., & Böckmann, A. (2015). Alternative salt bridge formation in Aβ-a hallmark of early-onset Alzheimer's disease?. Frontiers in molecular biosciences, 214. https://doi.org/10.3389/fmolb.2015.00014
Schledorn, Maarten, et al. "Alternative salt bridge formation in Aβ-a hallmark of early-onset Alzheimer's disease?." Frontiers in molecular biosciences vol. 2 (2015): 14. doi: https://doi.org/10.3389/fmolb.2015.00014
Schledorn M, Meier BH, Böckmann A. Alternative salt bridge formation in Aβ-a hallmark of early-onset Alzheimer's disease?. Front Mol Biosci. 2015 Apr 28;2:14. doi: 10.3389/fmolb.2015.00014. eCollection 2015. PMID: 25988181; PMCID: PMC4429654.
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Front Mol Biosci. 2015 Apr 28;2:14. doi: 10.3389/fmolb.2015.00014. eCollection 2015.

Alternative salt bridge formation in Aβ-a hallmark of early-onset Alzheimer's disease?.

Frontiers in molecular biosciences

Maarten Schledorn, Beat H Meier, Anja Böckmann

Affiliations

  1. Physical Chemistry, Eidgenössische Technische Hochschule Zürich Zurich, Switzerland.
  2. Institut de Biologie et Chimie des Protéines, Bases Moléculaires et Structurales des Systèmes Infectieux, Labex Ecofect, UMR 5086 CNRS, Université de Lyon Lyon, France.

PMID: 25988181 PMCID: PMC4429654 DOI: 10.3389/fmolb.2015.00014

Abstract

Recently the 3D structure of the Osaka mutant form (E22Δ) of Amyloid-β1-40 has been determined. We here compare the NMR chemical-shift with the published shifts of a brain-seeded form of wild-type Aβ and suggest that the determined mutant fold is accessible to the wild-type protein as well, with small conformational adaptations which accommodate the E22 residue missing in the Osaka mutant. In addition, we illustrate how other mutants could also conform to this model. The stabilization of the N-terminal part of the protein via an intermolecular salt bridge to Lys28 may represent a common structural motif for the mutants which are related to early-onset Alzheimer disease. This feature might connect to the observed increased toxicity of the mutant forms compared to wild-type Aβ1-40, where the salt bridge involving Lys28 is intramolecular.

Keywords: 3D structure; Alzheimer's disease; Osaka mutant; amyloid-beta; solid-state NMR

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