A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.

The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention because it has been associated with a range of neurodegenerative conditions including Alzheimer's and Parkinson's diseases. We provide a description...

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Autores principales:	Stefan Auer, Filip Meersman, Christopher M Dobson, Michele Vendruscolo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6636c0f4164943c39dd866bfd1611f45
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id	oai:doaj.org-article:6636c0f4164943c39dd866bfd1611f45
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spelling	oai:doaj.org-article:6636c0f4164943c39dd866bfd1611f452021-11-25T05:41:58ZA generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.1553-734X1553-735810.1371/journal.pcbi.1000222https://doaj.org/article/6636c0f4164943c39dd866bfd1611f452008-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19008938/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention because it has been associated with a range of neurodegenerative conditions including Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate that the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Individual beta-sheets initially form with random orientations and subsequently tend to align into protofilaments as their lengths increase. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first-order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.Stefan AuerFilip MeersmanChristopher M DobsonMichele VendruscoloPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 4, Iss 11, p e1000222 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Stefan Auer Filip Meersman Christopher M Dobson Michele Vendruscolo A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.
description	The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention because it has been associated with a range of neurodegenerative conditions including Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate that the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Individual beta-sheets initially form with random orientations and subsequently tend to align into protofilaments as their lengths increase. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first-order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.
format	article
author	Stefan Auer Filip Meersman Christopher M Dobson Michele Vendruscolo
author_facet	Stefan Auer Filip Meersman Christopher M Dobson Michele Vendruscolo
author_sort	Stefan Auer
title	A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.
title_short	A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.
title_full	A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.
title_fullStr	A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.
title_full_unstemmed	A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.
title_sort	generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/6636c0f4164943c39dd866bfd1611f45
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A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates.

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