Abstract

Development of extracellular plaques characteristic of Alzheimer’s disease is related to aggregation of amyloid peptides. The Aβ-42 peptide is the most aggregation prone species, and some missense mutant forms increase this aggregation ability. Due to its poor solubility as monomer in aqueous solutions, Aβ-42 conformational transitions in water have been largely investigated by molecular dynamics. Here we report an all-atom molecular dynamics analysis of the Aβ-42 peptide in aqueous environment using as starting conformation a structure obtained in an isotropic, low-polarity medium, representing a plausible model for the membrane-bound species. While previous studies commonly show that Aβ-42 is largely unstructured in aqueous solution, here we report that this peptide can adopt partially folded structures. Importance of ionic strength has been also investigated, showing that at physiological ionic strength condition a loop stabilizing electrostatic interaction involving Lys28 builds-up. In addition, beside stable α-helix structures, we observe the appearance of 310 helix, similar to what reported experimentally for the Aβ-40 species. The effect of E22Q (Dutch) mutation in high ionic strength condition has been explored. We show that this mutation has a dramatic impact on the Aβ-42 structure. Instead of a partially folded, but extended, conformation obtained with the wild type, the E22Q assumes a two-helix collapsed one due to the clustering of hydrophobic residues.

Autore Pugliese

• Palese Luigi Leonardo

Tutti gli autori

• PALESE L.L.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2013

ISSN

1570-9639

ISBN

Non Disponibile

Numero di citazioni Wos

12

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

13

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile