Ring-like N-fold Models of Aβ42 fibrils

Abstract When assembling as fibrils Aβ40 peptides can only assume U-shaped conformations while Aβ42 can also arrange as S-shaped three-stranded chains. We show that this allows Aβ42 peptides to assemble pore-like structures that may explain their higher toxicity. For this purpose, we develop a scala...

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Autores principales:	Wenhui Xi, Ulrich H. E. Hansmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/686e3a39388349e3b3af1e48edb6fece
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spelling	oai:doaj.org-article:686e3a39388349e3b3af1e48edb6fece2021-12-02T16:06:00ZRing-like N-fold Models of Aβ42 fibrils10.1038/s41598-017-06846-02045-2322https://doaj.org/article/686e3a39388349e3b3af1e48edb6fece2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06846-0https://doaj.org/toc/2045-2322Abstract When assembling as fibrils Aβ40 peptides can only assume U-shaped conformations while Aβ42 can also arrange as S-shaped three-stranded chains. We show that this allows Aβ42 peptides to assemble pore-like structures that may explain their higher toxicity. For this purpose, we develop a scalable model of ring-like assemblies of S-shaped Aβ1–42 chains and study the stability and structural properties of these assemblies through atomistic molecular dynamics simulations. We find that the proposed arrangements are in size and symmetry compatible with experimentally observed Aβ assemblies. We further show that the interior pore in our models allows for water leakage as a possible mechanism of cell toxicity of Aβ42 amyloids.Wenhui XiUlrich H. E. HansmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wenhui Xi Ulrich H. E. Hansmann Ring-like N-fold Models of Aβ42 fibrils
description	Abstract When assembling as fibrils Aβ40 peptides can only assume U-shaped conformations while Aβ42 can also arrange as S-shaped three-stranded chains. We show that this allows Aβ42 peptides to assemble pore-like structures that may explain their higher toxicity. For this purpose, we develop a scalable model of ring-like assemblies of S-shaped Aβ1–42 chains and study the stability and structural properties of these assemblies through atomistic molecular dynamics simulations. We find that the proposed arrangements are in size and symmetry compatible with experimentally observed Aβ assemblies. We further show that the interior pore in our models allows for water leakage as a possible mechanism of cell toxicity of Aβ42 amyloids.
format	article
author	Wenhui Xi Ulrich H. E. Hansmann
author_facet	Wenhui Xi Ulrich H. E. Hansmann
author_sort	Wenhui Xi
title	Ring-like N-fold Models of Aβ42 fibrils
title_short	Ring-like N-fold Models of Aβ42 fibrils
title_full	Ring-like N-fold Models of Aβ42 fibrils
title_fullStr	Ring-like N-fold Models of Aβ42 fibrils
title_full_unstemmed	Ring-like N-fold Models of Aβ42 fibrils
title_sort	ring-like n-fold models of aβ42 fibrils
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/686e3a39388349e3b3af1e48edb6fece
work_keys_str_mv	AT wenhuixi ringlikenfoldmodelsofab42fibrils AT ulrichhehansmann ringlikenfoldmodelsofab42fibrils
_version_	1718385153312555008

Ring-like N-fold Models of Aβ42 fibrils

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