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Distinct phases of free α-synuclein - A Monte Carlo study.

Jonsson, Sigurdur LU ; Mohanty, Sandipan and Irbäck, Anders LU (2012) In Proteins 80(9). p.2169-2177
Abstract
The α-synuclein protein (αS), implicated in Parkinson's disease (PD), shows conformational versatility. It aggregates into β-sheet-rich fibrils, occurs in helical membrane-bound forms, is disordered as a free monomer, and has recently been suggested to have a folded helical tetramer as its main physiological form. Here we use implicit solvent all-atom Monte Carlo (MC) methods to explore the conformational ensemble sampled by the free αS monomer. We analyze secondary-structure propensities, size and topological properties, and compare with existing experimental data. Our study suggests that free αS has two distinct phases. One phase has the expected disordered character. The other phase also shows large conformational variability. However,... (More)
The α-synuclein protein (αS), implicated in Parkinson's disease (PD), shows conformational versatility. It aggregates into β-sheet-rich fibrils, occurs in helical membrane-bound forms, is disordered as a free monomer, and has recently been suggested to have a folded helical tetramer as its main physiological form. Here we use implicit solvent all-atom Monte Carlo (MC) methods to explore the conformational ensemble sampled by the free αS monomer. We analyze secondary-structure propensities, size and topological properties, and compare with existing experimental data. Our study suggests that free αS has two distinct phases. One phase has the expected disordered character. The other phase also shows large conformational variability. However, in this phase, the β-strand content is substantial, and the backbone fold shows statistical similarities with that in αS fibrils. Presence of this phase is consistent with data from low-temperature experiments. Conversion of disordered αS to this fibril-like form requires the crossing of a rather large apparent free-energy barrier. Proteins 2012. © 2012 Wiley Periodicals, Inc. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amyloid, conformational heterogeneity, protein aggregation, protein folding, protein misfolding
in
Proteins
volume
80
issue
9
pages
2169 - 2177
publisher
John Wiley & Sons
external identifiers
  • wos:000306962300004
  • pmid:22552968
  • scopus:84864415168
ISSN
0887-3585
DOI
10.1002/prot.24107
language
English
LU publication?
yes
id
4c8eaa3a-25f2-409b-81b3-e6ed364418f1 (old id 2609224)
date added to LUP
2012-08-10 12:11:07
date last changed
2017-04-23 04:00:07
@article{4c8eaa3a-25f2-409b-81b3-e6ed364418f1,
  abstract     = {The α-synuclein protein (αS), implicated in Parkinson's disease (PD), shows conformational versatility. It aggregates into β-sheet-rich fibrils, occurs in helical membrane-bound forms, is disordered as a free monomer, and has recently been suggested to have a folded helical tetramer as its main physiological form. Here we use implicit solvent all-atom Monte Carlo (MC) methods to explore the conformational ensemble sampled by the free αS monomer. We analyze secondary-structure propensities, size and topological properties, and compare with existing experimental data. Our study suggests that free αS has two distinct phases. One phase has the expected disordered character. The other phase also shows large conformational variability. However, in this phase, the β-strand content is substantial, and the backbone fold shows statistical similarities with that in αS fibrils. Presence of this phase is consistent with data from low-temperature experiments. Conversion of disordered αS to this fibril-like form requires the crossing of a rather large apparent free-energy barrier. Proteins 2012. © 2012 Wiley Periodicals, Inc.},
  author       = {Jonsson, Sigurdur and Mohanty, Sandipan and Irbäck, Anders},
  issn         = {0887-3585},
  keyword      = {amyloid,conformational heterogeneity,protein aggregation,protein folding,protein misfolding},
  language     = {eng},
  number       = {9},
  pages        = {2169--2177},
  publisher    = {John Wiley & Sons},
  series       = {Proteins},
  title        = {Distinct phases of free α-synuclein - A Monte Carlo study.},
  url          = {http://dx.doi.org/10.1002/prot.24107},
  volume       = {80},
  year         = {2012},
}