Stability and structure of oligomers of the Alzheimer peptide Abeta16-22: from the dimer to the 32-mer.

Détails

ID Serval
serval:BIB_4D9807BB0443
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Stability and structure of oligomers of the Alzheimer peptide Abeta16-22: from the dimer to the 32-mer.
Périodique
Biophysical Journal
Auteur(s)
Röhrig U.F., Laio A., Tantalo N., Parrinello M., Petronzio R.
ISSN
0006-3495 (Print)
ISSN-L
0006-3495
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
91
Numéro
9
Pages
3217-3229
Langue
anglais
Notes
Corresponding Author: Röhrig, Ute F.
Résumé
Several neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases are associated with amyloid fibrils formed by different polypeptides. We probe the structure and stability of oligomers of different sizes of the fragment Abeta(16-22) of the Alzheimer beta-amyloid peptide using atomic-detail molecular dynamics simulations with explicit solvent. We find that only large oligomers form a stable beta-sheet aggregate, the minimum nucleus size being of the order of 8-16 peptides. This effect is attributed to better hydrophobic contacts and a better shielding of backbone-backbone hydrogen bonds from the solvent in bigger assemblies. Moreover, the observed stability of beta-sheet aggregates with a different number of layers can be explained on the basis of their solvent-accessible surface area. Depending on the stacking interface between the sheets, we observe straight or twisted structures, which could be linked to the experimentally observed polymorphism of amyloid fibrils. To compare our 32-mer structure to experimental data, we calculate its x-ray diffraction pattern. Good agreement is found between experimentally and theoretically determined reflections, suggesting that our model indeed closely resembles the structures found in vitro.
Mots-clé
Amyloid beta-Peptides/chemistry, Computer Simulation, Dimerization, Drug Stability, Models, Chemical, Models, Molecular, Multiprotein Complexes/chemistry, Multiprotein Complexes/ultrastructure, Peptide Fragments/chemistry, Protein Conformation, Protein Denaturation
Pubmed
Web of science
Open Access
Oui
Création de la notice
30/10/2015 9:12
Dernière modification de la notice
20/08/2019 14:02
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