Structural characteristics and membrane interactions of tandem α-synuclein oligomers

Abstract Pre-fibrillar oligomers of α-synuclein are thought to be pathogenic molecules leading to neurotoxicity associated with Parkinson’s disease and other neurodegenerative disorders. However, small oligomers are difficult to isolate for study. To gain better insight into the properties of small...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chunhua Dong, Marion Hoffmann, Xi Li, Meijing Wang, Craig R. Garen, Nils O. Petersen, Michael T. Woodside
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/753ab479bd164e23b8bc169e752047c5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:753ab479bd164e23b8bc169e752047c5
record_format	dspace
spelling	oai:doaj.org-article:753ab479bd164e23b8bc169e752047c52021-12-02T12:32:47ZStructural characteristics and membrane interactions of tandem α-synuclein oligomers10.1038/s41598-018-25133-02045-2322https://doaj.org/article/753ab479bd164e23b8bc169e752047c52018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25133-0https://doaj.org/toc/2045-2322Abstract Pre-fibrillar oligomers of α-synuclein are thought to be pathogenic molecules leading to neurotoxicity associated with Parkinson’s disease and other neurodegenerative disorders. However, small oligomers are difficult to isolate for study. To gain better insight into the properties of small α-synuclein oligomers, we investigated engineered oligomers of specific size (dimers, tetramers, and octamers) linked head-to-tail in tandem, comparing the behavior of the oligomers to monomeric α-synuclein. All oligomeric constructs remained largely disordered in solution, as determined from dynamic light scattering and size-exclusion chromatography. Electron microscopy revealed that each construct could aggregate to form fibrils similar to those formed by monomeric α-synuclein. The interactions with large unilamellar vesicles (LUVs) composed of negatively-charged lipids differed depending on size, with smaller oligomers forming more extensive helical structure as determined by CD spectroscopy. Monitoring the influx of a fluorescence bleaching agent into vesicles showed that larger oligomers were somewhat more effective at degrading vesicular integrity and inducing membrane permeabilization.Chunhua DongMarion HoffmannXi LiMeijing WangCraig R. GarenNils O. PetersenMichael T. WoodsideNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chunhua Dong Marion Hoffmann Xi Li Meijing Wang Craig R. Garen Nils O. Petersen Michael T. Woodside Structural characteristics and membrane interactions of tandem α-synuclein oligomers
description	Abstract Pre-fibrillar oligomers of α-synuclein are thought to be pathogenic molecules leading to neurotoxicity associated with Parkinson’s disease and other neurodegenerative disorders. However, small oligomers are difficult to isolate for study. To gain better insight into the properties of small α-synuclein oligomers, we investigated engineered oligomers of specific size (dimers, tetramers, and octamers) linked head-to-tail in tandem, comparing the behavior of the oligomers to monomeric α-synuclein. All oligomeric constructs remained largely disordered in solution, as determined from dynamic light scattering and size-exclusion chromatography. Electron microscopy revealed that each construct could aggregate to form fibrils similar to those formed by monomeric α-synuclein. The interactions with large unilamellar vesicles (LUVs) composed of negatively-charged lipids differed depending on size, with smaller oligomers forming more extensive helical structure as determined by CD spectroscopy. Monitoring the influx of a fluorescence bleaching agent into vesicles showed that larger oligomers were somewhat more effective at degrading vesicular integrity and inducing membrane permeabilization.
format	article
author	Chunhua Dong Marion Hoffmann Xi Li Meijing Wang Craig R. Garen Nils O. Petersen Michael T. Woodside
author_facet	Chunhua Dong Marion Hoffmann Xi Li Meijing Wang Craig R. Garen Nils O. Petersen Michael T. Woodside
author_sort	Chunhua Dong
title	Structural characteristics and membrane interactions of tandem α-synuclein oligomers
title_short	Structural characteristics and membrane interactions of tandem α-synuclein oligomers
title_full	Structural characteristics and membrane interactions of tandem α-synuclein oligomers
title_fullStr	Structural characteristics and membrane interactions of tandem α-synuclein oligomers
title_full_unstemmed	Structural characteristics and membrane interactions of tandem α-synuclein oligomers
title_sort	structural characteristics and membrane interactions of tandem α-synuclein oligomers
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/753ab479bd164e23b8bc169e752047c5
work_keys_str_mv	AT chunhuadong structuralcharacteristicsandmembraneinteractionsoftandemasynucleinoligomers AT marionhoffmann structuralcharacteristicsandmembraneinteractionsoftandemasynucleinoligomers AT xili structuralcharacteristicsandmembraneinteractionsoftandemasynucleinoligomers AT meijingwang structuralcharacteristicsandmembraneinteractionsoftandemasynucleinoligomers AT craigrgaren structuralcharacteristicsandmembraneinteractionsoftandemasynucleinoligomers AT nilsopetersen structuralcharacteristicsandmembraneinteractionsoftandemasynucleinoligomers AT michaeltwoodside structuralcharacteristicsandmembraneinteractionsoftandemasynucleinoligomers
_version_	1718393987019046912

Structural characteristics and membrane interactions of tandem α-synuclein oligomers

Ejemplares similares