Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy

Abstract The amyloid-beta peptide (Aβ) plays a major role in the progression of Alzheimer’s disease. Due to its high toxicity, the 42 amino acid long isoform Aβ42 has become of considerable interest. The Aβ42 monomer is prone to aggregation down to the nanomolar range which makes conventional struct...

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Autores principales:	Mario Schneider, Stefan Walta, Chris Cadek, Walter Richtering, Dieter Willbold
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ff9409479d443f6a63b16bf13b01ca1
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spelling	oai:doaj.org-article:0ff9409479d443f6a63b16bf13b01ca12021-12-02T12:32:54ZFluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy10.1038/s41598-017-02410-y2045-2322https://doaj.org/article/0ff9409479d443f6a63b16bf13b01ca12017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02410-yhttps://doaj.org/toc/2045-2322Abstract The amyloid-beta peptide (Aβ) plays a major role in the progression of Alzheimer’s disease. Due to its high toxicity, the 42 amino acid long isoform Aβ42 has become of considerable interest. The Aβ42 monomer is prone to aggregation down to the nanomolar range which makes conventional structural methods such as NMR or X-ray crystallography infeasible. Conformational information, however, will be helpful to understand the different aggregation pathways reported in the literature and will allow to identify potential conditions that favour aggregation-incompetent conformations. In this study, we applied fluorescence correlation spectroscopy (FCS) to investigate the unfolding of Alexa Fluor 488 labelled monomeric Aβ42 using guanidine hydrochloride as a denaturant. We show that our Aβ42 pre-treatment and the low-nanomolar concentrations, typically used for FCS measurements, strongly favour the presence of monomers. Our results reveal that there is an unfolding/folding behaviour of monomeric Aβ42. The existence of a cooperative unfolding curve suggests the presence of structural elements with a Gibbs free energy of unfolding of about 2.8 kcal/mol.Mario SchneiderStefan WaltaChris CadekWalter RichteringDieter WillboldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mario Schneider Stefan Walta Chris Cadek Walter Richtering Dieter Willbold Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy
description	Abstract The amyloid-beta peptide (Aβ) plays a major role in the progression of Alzheimer’s disease. Due to its high toxicity, the 42 amino acid long isoform Aβ42 has become of considerable interest. The Aβ42 monomer is prone to aggregation down to the nanomolar range which makes conventional structural methods such as NMR or X-ray crystallography infeasible. Conformational information, however, will be helpful to understand the different aggregation pathways reported in the literature and will allow to identify potential conditions that favour aggregation-incompetent conformations. In this study, we applied fluorescence correlation spectroscopy (FCS) to investigate the unfolding of Alexa Fluor 488 labelled monomeric Aβ42 using guanidine hydrochloride as a denaturant. We show that our Aβ42 pre-treatment and the low-nanomolar concentrations, typically used for FCS measurements, strongly favour the presence of monomers. Our results reveal that there is an unfolding/folding behaviour of monomeric Aβ42. The existence of a cooperative unfolding curve suggests the presence of structural elements with a Gibbs free energy of unfolding of about 2.8 kcal/mol.
format	article
author	Mario Schneider Stefan Walta Chris Cadek Walter Richtering Dieter Willbold
author_facet	Mario Schneider Stefan Walta Chris Cadek Walter Richtering Dieter Willbold
author_sort	Mario Schneider
title	Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy
title_short	Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy
title_full	Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy
title_fullStr	Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy
title_full_unstemmed	Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy
title_sort	fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low gibbs free energy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0ff9409479d443f6a63b16bf13b01ca1
work_keys_str_mv	AT marioschneider fluorescencecorrelationspectroscopyrevealsacooperativeunfoldingofmonomericamyloidb42withalowgibbsfreeenergy AT stefanwalta fluorescencecorrelationspectroscopyrevealsacooperativeunfoldingofmonomericamyloidb42withalowgibbsfreeenergy AT chriscadek fluorescencecorrelationspectroscopyrevealsacooperativeunfoldingofmonomericamyloidb42withalowgibbsfreeenergy AT walterrichtering fluorescencecorrelationspectroscopyrevealsacooperativeunfoldingofmonomericamyloidb42withalowgibbsfreeenergy AT dieterwillbold fluorescencecorrelationspectroscopyrevealsacooperativeunfoldingofmonomericamyloidb42withalowgibbsfreeenergy
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Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy

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