Alkali ion influence on structure and stability of fibrillar amyloid-β oligomers

  • Danyil Huraskin
  • Anselm H. C. HornEmail author
Original Paper
Part of the following topical collections:
  1. Tim Clark 70th Birthday Festschrift


Alzheimer’s disease is characterized by the aggregation of Amyloid-β (Aβ) peptide into oligomers, fibrils and plaques. Many factors influencing this process as well as the stability of the various Aβ aggregates are known to date, and include the concentration and type of metal ions. Most experimental and theoretical studies have concentrated on heavy metal ions, like Fe2+, Zn2+, or Cu2+, while the smaller alkali ions Li+, Na+, and K+ have not gained much attention notwithstanding their role and ubiquity in physiological environments. In this work, we applied atomistic molecular dynamics simulations to investigate the potential role of these alkali ions in stabilizing fibrillar Aβ oligomers of different size and topology, i.e., single and double filament systems comprising 3–24 peptide chains per filament. We find a pronounced difference on the molecular level in the interaction behavior with free carboxylate groups of the Aβ oligomer: Li+ forms stable bridged interactions, whereas K+ interacts more transiently and lacks bridging. The behavior of Na+ is in between, so that this ion–protein interaction obeys the renowned Hofmeister series. These differences are also reflected in the ability of the alkali ions to stabilize the oligomer secondary structure. The stabilizing effect is most pronounced for the smaller fibrillar oligomers, suggesting that the type of alkali ion critically affects the initial stages of fibril formation. Our findings thus offer a molecular explanation for the observation that the polymorphisms of Aβ fibril structures are caused by differences in the surrounding ionic environment.

Graphical abstract

Influence of alkali ions on the structure and stability of fibrillar amyloid-β oligomers


Molecular dynamics simulations Sodium-effect Alzheimer’s disease Lithium Potassium Hofmeister series 



This work was supported by the Alzheimer Forschung Initiative e.V. (AFI) via a Pilot Grant (#12858). A.H.C.H. thanks the Leibniz-Rechenzentrum (LRZ) München for granting access to its GPU cluster and Heinrich Sticht for many fruitful discussions. Additionally, the authors gratefully acknowledge the compute resources (GPU and CPU cluster) and support provided by the Erlangen Regional Computing Center (RRZE).

Supplementary material

894_2018_3920_MOESM1_ESM.pdf (1.4 mb)
Online Resource 1 Document (pdf format) with representations of the final simulation structures of a2x03, a2x06, a2x24, a1x06, and a1x24 (Fig. S1–S5), flexibility difference at the fibril ends (Fig. S6), and plots of the evolution of the ion coordination in a2x12 to E22 (Fig. S7). (PDF 1435 kb)
894_2018_3920_MOESM2_ESM.mpg (5.4 mb)
Online Resource 2 Movie (mpg format) of MD simulation trajectory of 150 mM Na+ with a2x12 (JC parameters, run1, 200 ns); for clarity, only one filament is shown in secondary structure representation with E11, E22, D23, and A42 depicted in red sticks and Na+ ions within 5 Å of the filament as blue spheres. The protein movement is smoothed via VMD. (MPG 5389 kb)
894_2018_3920_MOESM3_ESM.mpg (5.3 mb)
Online Resource 3 Movie (mpg format) of MD simulation trajectory of 150 mM K+ with a2x12 (JC parameters, run1, 200 ns); for clarity, only one filament is shown in secondary structure representation with E11, E22, D23, and A42 depicted in red sticks and K+ ions within 5 Å of the filament as violet spheres. The protein movement is smoothed via VMD. (MPG 5387 kb)
894_2018_3920_MOESM4_ESM.mpg (5.3 mb)
Online Resource 4 Movie (mpg format) of MD simulation trajectory of 150 mM Li+ with a2x12 (JC parameters, run1, 200 ns); for clarity, only one filament is shown in secondary structure representation with E11, E22, D23, and A42 depicted in red sticks and Li+ ions within 5 Å of the filament as iceblue spheres. The protein movement is smoothed via VMD. (MPG 5519 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Bioinformatik Institut für Biochemie Emil-Fischer-ZentrumFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

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