A multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.

The self-organization of peptides into amyloidogenic oligomers is one of the key events for a wide range of molecular and degenerative diseases. Atomic-resolution characterization of the mechanisms responsible for the aggregation process and the resulting structures is thus a necessary step to impro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jessica Nasica-Labouze, Massimiliano Meli, Philippe Derreumaux, Giorgio Colombo, Normand Mousseau
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/559c8a4cc7db4387a599421f4ca6e3ec
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:559c8a4cc7db4387a599421f4ca6e3ec
record_format	dspace
spelling	oai:doaj.org-article:559c8a4cc7db4387a599421f4ca6e3ec2021-11-18T05:50:32ZA multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.1553-734X1553-735810.1371/journal.pcbi.1002051https://doaj.org/article/559c8a4cc7db4387a599421f4ca6e3ec2011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21625573/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The self-organization of peptides into amyloidogenic oligomers is one of the key events for a wide range of molecular and degenerative diseases. Atomic-resolution characterization of the mechanisms responsible for the aggregation process and the resulting structures is thus a necessary step to improve our understanding of the determinants of these pathologies. To address this issue, we combine the accelerated sampling properties of replica exchange molecular dynamics simulations based on the OPEP coarse-grained potential with the atomic resolution description of interactions provided by all-atom MD simulations, and investigate the oligomerization process of the GNNQQNY for three system sizes: 3-mers, 12-mers and 20-mers. Results for our integrated simulations show a rich variety of structural arrangements for aggregates of all sizes. Elongated fibril-like structures can form transiently in the 20-mer case, but they are not stable and easily interconvert in more globular and disordered forms. Our extensive characterization of the intermediate structures and their physico-chemical determinants points to a high degree of polymorphism for the GNNQQNY sequence that can be reflected at the macroscopic scale. Detailed mechanisms and structures that underlie amyloid aggregation are also provided.Jessica Nasica-LabouzeMassimiliano MeliPhilippe DerreumauxGiorgio ColomboNormand MousseauPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 5, p e1002051 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jessica Nasica-Labouze Massimiliano Meli Philippe Derreumaux Giorgio Colombo Normand Mousseau A multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.
description	The self-organization of peptides into amyloidogenic oligomers is one of the key events for a wide range of molecular and degenerative diseases. Atomic-resolution characterization of the mechanisms responsible for the aggregation process and the resulting structures is thus a necessary step to improve our understanding of the determinants of these pathologies. To address this issue, we combine the accelerated sampling properties of replica exchange molecular dynamics simulations based on the OPEP coarse-grained potential with the atomic resolution description of interactions provided by all-atom MD simulations, and investigate the oligomerization process of the GNNQQNY for three system sizes: 3-mers, 12-mers and 20-mers. Results for our integrated simulations show a rich variety of structural arrangements for aggregates of all sizes. Elongated fibril-like structures can form transiently in the 20-mer case, but they are not stable and easily interconvert in more globular and disordered forms. Our extensive characterization of the intermediate structures and their physico-chemical determinants points to a high degree of polymorphism for the GNNQQNY sequence that can be reflected at the macroscopic scale. Detailed mechanisms and structures that underlie amyloid aggregation are also provided.
format	article
author	Jessica Nasica-Labouze Massimiliano Meli Philippe Derreumaux Giorgio Colombo Normand Mousseau
author_facet	Jessica Nasica-Labouze Massimiliano Meli Philippe Derreumaux Giorgio Colombo Normand Mousseau
author_sort	Jessica Nasica-Labouze
title	A multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.
title_short	A multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.
title_full	A multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.
title_fullStr	A multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.
title_full_unstemmed	A multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.
title_sort	multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide gnnqqny from the yeast prion sup-35.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/559c8a4cc7db4387a599421f4ca6e3ec
work_keys_str_mv	AT jessicanasicalabouze amultiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT massimilianomeli amultiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT philippederreumaux amultiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT giorgiocolombo amultiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT normandmousseau amultiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT jessicanasicalabouze multiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT massimilianomeli multiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT philippederreumaux multiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT giorgiocolombo multiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35 AT normandmousseau multiscaleapproachtocharacterizetheearlyaggregationstepsoftheamyloidformingpeptidegnnqqnyfromtheyeastprionsup35
_version_	1718424785753473024

A multiscale approach to characterize the early aggregation steps of the amyloid-forming peptide GNNQQNY from the yeast prion sup-35.

Ejemplares similares