Mechanical resistance in unstructured proteins.
Jonsson, Sigurdur LU ; Mitternacht, Simon LU and Irbäck, Anders LU
(2013)
In Biophysical Journal
104(12).
p.2725-2732
- Abstract
- 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.... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3913061
- author
- Jonsson, Sigurdur
LU
; Mitternacht, Simon
LU
and Irbäck, Anders
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biophysical Journal
- volume
- 104
- issue
- 12
- pages
- 2725 - 2732
- publisher
- Cell Press
- external identifiers
-
- wos:000320757100018
- pmid:23790381
- scopus:84879223193
- ISSN
- 1542-0086
- DOI
- 10.1016/j.bpj.2013.05.003
- language
- English
- LU publication?
- yes
- id
- 0d8769aa-6fb9-459f-87de-2645b535bbcd (old id 3913061)
- date added to LUP
- 2016-04-01 10:38:19
- date last changed
- 2024-01-21 18:44:11
@article{0d8769aa-6fb9-459f-87de-2645b535bbcd,
abstract = {{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.}},
author = {{Jonsson, Sigurdur and Mitternacht, Simon and Irbäck, Anders}},
issn = {{1542-0086}},
language = {{eng}},
number = {{12}},
pages = {{2725--2732}},
publisher = {{Cell Press}},
series = {{Biophysical Journal}},
title = {{Mechanical resistance in unstructured proteins.}},
url = {{http://dx.doi.org/10.1016/j.bpj.2013.05.003}},
doi = {{10.1016/j.bpj.2013.05.003}},
volume = {{104}},
year = {{2013}},
}