Anders Irbäck
Professor
Mechanical resistance in unstructured proteins.
Författare
Summary, in English
Single-molecule pulling experiments on unstructured proteins linked to neurodegenerative diseases have measured rupture forces comparable to those for stable folded proteins. To investigate the structural mechanisms of this unexpected force resistance, we perform pulling simulations of the amyloid β-peptide (Aβ) and α-synuclein (αS), starting from simulated conformational ensembles for the free monomers. For both proteins, the simulations yield a set of rupture events that agree well with the experimental data. By analyzing the conformations occurring shortly before rupture in each event, we find that the mechanically resistant structures share a common architecture, with similarities to the folds adopted by Aβ and αS in amyloid fibrils. The disease-linked Arctic mutation of Aβ is found to increase the occurrence of highly force-resistant structures. Our study suggests that the high rupture forces observed in Aβ and αS pulling experiments are caused by structures that might have a key role in amyloid formation.
Avdelning/ar
- Beräkningsbiologi och biologisk fysik - Har omorganiserats
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
Publiceringsår
2013
Språk
Engelska
Sidor
2725-2732
Publikation/Tidskrift/Serie
Biophysical Journal
Volym
104
Issue
12
Dokumenttyp
Artikel i tidskrift
Förlag
Cell Press
Ämne
- Other Physics Topics
- Biophysics
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1542-0086