Journal Article

PreJuSER-21248

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Distinct phases of free a-synuclein - A Monte Carlo study

Jónsson, S. A. ; Mohanty, S.FZJ* ; Irbäck, A.

2012
Wiley-Liss New York, NY

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Please use a persistent id in citations: doi:10.1002/prot.24107

Abstract: The α-synuclein protein (αS), implicated in Parkinson's disease, 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 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.

Keyword(s): J ; protein folding (auto) ; protein misfolding (auto) ; protein aggregation (auto) ; amyloid (auto) ; conformational heterogeneity (auto)

Note: Grant sponsor: Swedish National Infrastructure for Computing; Grant number: SNIC 001/11-130; Grant sponsor: Julich Supercomputing Centre; Grant number: JJSC 03.

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Contributing Institute(s):

1. Jülich Supercomputing Centre (JSC)

Research Program(s):

1. Scientific Computing (FUEK411) (FUEK411)
2. 411 - Computational Science and Mathematical Methods (POF2-411) (POF2-411)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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