Comparing the folding free-energy landscapes of Abeta42 variants with different aggregation properties.
Mitternacht, Simon LU ; Staneva, Iskra LU ; Härd, Torleif and Irbäck, Anders LU
(2010)
In Proteins
78(12).
p.2600-2608
- Abstract
- The properties of the amyloid-beta peptide that lead to aggregation associated with Alzheimer's disease are not fully understood. This study aims at identifying conformational differences among four variants of full-length Abeta42 that are known to display very different aggregation properties. By extensive all-atom Monte Carlo simulations, we find that a variety of beta-sheet structures with distinct turns are readily accessible for full-length Abeta42. In the simulations, wild type (WT) Abeta42 preferentially populates two major classes of conformations, either extended with high beta-sheet content or more compact with lower beta-sheet content. The three mutations studied alter the balance between these classes. Strong mutational effects... (More)
- The properties of the amyloid-beta peptide that lead to aggregation associated with Alzheimer's disease are not fully understood. This study aims at identifying conformational differences among four variants of full-length Abeta42 that are known to display very different aggregation properties. By extensive all-atom Monte Carlo simulations, we find that a variety of beta-sheet structures with distinct turns are readily accessible for full-length Abeta42. In the simulations, wild type (WT) Abeta42 preferentially populates two major classes of conformations, either extended with high beta-sheet content or more compact with lower beta-sheet content. The three mutations studied alter the balance between these classes. Strong mutational effects are observed in a region centered at residues 23-26, where WT Abeta42 tends to form a turn. The aggregation-accelerating E22G mutation associated with early onset of Alzheimer's disease makes this turn region conformationally more diverse, whereas the aggregation-decelerating F20E mutation has the reverse effect, and the E22G/I31E mutation reduces the turn population. Comparing results for the four Abeta42 variants, we identify specific conformational properties of residues 23-26 that might play a key role in aggregation. Proteins 2010. (c) 2010 Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1645446
- author
- Mitternacht, Simon
LU
; Staneva, Iskra
LU
; Härd, Torleif
and Irbäck, Anders
LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- mutations, amyloid-beta, all atom, implicit solvent, Monte Carlo, J-coupling constants, chemical shifts
- in
- Proteins
- volume
- 78
- issue
- 12
- pages
- 2600 - 2608
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000280822000003
- pmid:20589631
- scopus:77955790562
- pmid:20589631
- ISSN
- 0887-3585
- DOI
- 10.1002/prot.22775
- language
- English
- LU publication?
- yes
- id
- 5a663388-83f2-4c4f-8e46-9427885d1b59 (old id 1645446)
- date added to LUP
- 2016-04-01 14:25:38
- date last changed
- 2024-01-10 03:41:18
@article{5a663388-83f2-4c4f-8e46-9427885d1b59,
abstract = {{The properties of the amyloid-beta peptide that lead to aggregation associated with Alzheimer's disease are not fully understood. This study aims at identifying conformational differences among four variants of full-length Abeta42 that are known to display very different aggregation properties. By extensive all-atom Monte Carlo simulations, we find that a variety of beta-sheet structures with distinct turns are readily accessible for full-length Abeta42. In the simulations, wild type (WT) Abeta42 preferentially populates two major classes of conformations, either extended with high beta-sheet content or more compact with lower beta-sheet content. The three mutations studied alter the balance between these classes. Strong mutational effects are observed in a region centered at residues 23-26, where WT Abeta42 tends to form a turn. The aggregation-accelerating E22G mutation associated with early onset of Alzheimer's disease makes this turn region conformationally more diverse, whereas the aggregation-decelerating F20E mutation has the reverse effect, and the E22G/I31E mutation reduces the turn population. Comparing results for the four Abeta42 variants, we identify specific conformational properties of residues 23-26 that might play a key role in aggregation. Proteins 2010. (c) 2010 Wiley-Liss, Inc.}},
author = {{Mitternacht, Simon and Staneva, Iskra and Härd, Torleif and Irbäck, Anders}},
issn = {{0887-3585}},
keywords = {{mutations; amyloid-beta; all atom; implicit solvent; Monte Carlo; J-coupling constants; chemical shifts}},
language = {{eng}},
number = {{12}},
pages = {{2600--2608}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Proteins}},
title = {{Comparing the folding free-energy landscapes of Abeta42 variants with different aggregation properties.}},
url = {{http://dx.doi.org/10.1002/prot.22775}},
doi = {{10.1002/prot.22775}},
volume = {{78}},
year = {{2010}},
}