Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Anders Irbäck. Photo.

Anders Irbäck

Professor

Anders Irbäck. Photo.

Mechanical resistance in unstructured proteins.

Author

  • Sigurdur Jonsson
  • Simon Mitternacht
  • Anders Irbäck

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.

Department/s

  • Computational Biology and Biological Physics
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease

Publishing year

2013

Language

English

Pages

2725-2732

Publication/Series

Biophysical Journal

Volume

104

Issue

12

Document type

Journal article

Publisher

Cell Press

Topic

  • Other Physics Topics
  • Biophysics

Status

Published

ISBN/ISSN/Other

  • ISSN: 1542-0086