The impact of water on the ambivalent behavior and paradoxical phenomenon of the amyloid-β fibril protein

Tamás Vajda, A. Perczel

Research output: Contribution to journalArticle

Abstract

The crucial role of water in amyloid-β(Aβ) fibril proteins is evaluated in several ways including the water's thermodynamic and kinetic solvation effects. As regards the water's character, its hindered-rotation barriers are also considered. The following protein molecules considered here are: the Aβ40 (PDB ID: 2LMN), Aβ42 (PDB ID: 5KK3 and 2NAO) and the double-layered Aβ17-42 fibril. We discuss: (i) extracellular Aβ40 and Aβ42 fibril monomers exhibit an ambivalent propensity to transform into a helical form toward the N-term region and a β-strand-like form near the C-terminal; (ii) interfacial water molecules play a crucial role in protein-protein interactions, as molecular dynamics simulations have shown a significant impact on the protein-protein binding; (iii) it is shown that the spontaneous dimerization process of the Aβ42 fibril protein in water occurs via a two-step nucleation-accommodation mechanism; (iv) MD simulations of the double-layered Aβ17-42 fibril model show that the C↔C interface appears more energetically favorable than the N↔N interface due to large hydrophobic contacts; (v) the water's role in the HET-s prion and in the Aβ fibrillar aggregates; (vi) it was found that the monomer-oligomer equilibrium spontaneously dissociates into stable monomeric species when they are incubated up to 3 μm for a longer time (>1 week) in a physiological buffer.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalBiomolecular Concepts
Volume8
Issue number5-6
DOIs
Publication statusPublished - Dec 20 2017

Fingerprint

Amyloidogenic Proteins
Amyloid
Water
A 17
Proteins
Monomers
Serum Amyloid A Protein
Molecules
Dimerization
Prions
Solvation
Molecular Dynamics Simulation
Thermodynamics
Oligomers
Protein Binding
Molecular dynamics
Buffers
Nucleation
Kinetics
Computer simulation

Keywords

  • ambivalent behavior
  • amyloid-β fibril protein
  • Aβ fibril formation
  • benign-toxic paradox
  • membrane affinity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cellular and Molecular Neuroscience

Cite this

The impact of water on the ambivalent behavior and paradoxical phenomenon of the amyloid-β fibril protein. / Vajda, Tamás; Perczel, A.

In: Biomolecular Concepts, Vol. 8, No. 5-6, 20.12.2017, p. 213-220.

Research output: Contribution to journalArticle

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