Nano-assembly of amyloid β peptide: role of the hairpin fold

Abstract Structural investigations have revealed that β hairpin structures are common features in amyloid fibrils, suggesting that these motifs play an important role in amyloid assembly. To test this hypothesis, we characterized the effect of the hairpin fold on the aggregation process using a mode...

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Autores principales:	Sibaprasad Maity, Mohtadin Hashemi, Yuri L. Lyubchenko
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/27bd31e827a34c1190ad6b96672f031f
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spelling	oai:doaj.org-article:27bd31e827a34c1190ad6b96672f031f2021-12-02T16:07:45ZNano-assembly of amyloid β peptide: role of the hairpin fold10.1038/s41598-017-02454-02045-2322https://doaj.org/article/27bd31e827a34c1190ad6b96672f031f2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02454-0https://doaj.org/toc/2045-2322Abstract Structural investigations have revealed that β hairpin structures are common features in amyloid fibrils, suggesting that these motifs play an important role in amyloid assembly. To test this hypothesis, we characterized the effect of the hairpin fold on the aggregation process using a model β hairpin structure, consisting of two Aβ(14–23) monomers connected by a turn forming YNGK peptide. AFM studies of the assembled aggregates revealed that the hairpin forms spherical structures whereas linear Aβ(14–23) monomers form fibrils. Additionally, an equimolar mixture of the monomer and the hairpin assembles into non-fibrillar aggregates, demonstrating that the hairpin fold dramatically changes the morphology of assembled amyloid aggregates. To understand the molecular mechanism underlying the role of the hairpin fold on amyloid assembly, we performed single-molecule probing experiments to measure interactions between hairpin and monomer and two hairpin complexes. The studies reveal that the stability of hairpin-monomer complexes is much higher than hairpin-hairpin complexes. Molecular dynamics simulations revealed a novel intercalated complex for the hairpin and monomer and Monte Carlo modeling further demonstrated that such nano-assemblies have elevated stability compared with stability of the dimer formed by Aβ(14–23) hairpin. The role of such folding on the amyloid assembly is also discussed.Sibaprasad MaityMohtadin HashemiYuri L. LyubchenkoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sibaprasad Maity Mohtadin Hashemi Yuri L. Lyubchenko Nano-assembly of amyloid β peptide: role of the hairpin fold
description	Abstract Structural investigations have revealed that β hairpin structures are common features in amyloid fibrils, suggesting that these motifs play an important role in amyloid assembly. To test this hypothesis, we characterized the effect of the hairpin fold on the aggregation process using a model β hairpin structure, consisting of two Aβ(14–23) monomers connected by a turn forming YNGK peptide. AFM studies of the assembled aggregates revealed that the hairpin forms spherical structures whereas linear Aβ(14–23) monomers form fibrils. Additionally, an equimolar mixture of the monomer and the hairpin assembles into non-fibrillar aggregates, demonstrating that the hairpin fold dramatically changes the morphology of assembled amyloid aggregates. To understand the molecular mechanism underlying the role of the hairpin fold on amyloid assembly, we performed single-molecule probing experiments to measure interactions between hairpin and monomer and two hairpin complexes. The studies reveal that the stability of hairpin-monomer complexes is much higher than hairpin-hairpin complexes. Molecular dynamics simulations revealed a novel intercalated complex for the hairpin and monomer and Monte Carlo modeling further demonstrated that such nano-assemblies have elevated stability compared with stability of the dimer formed by Aβ(14–23) hairpin. The role of such folding on the amyloid assembly is also discussed.
format	article
author	Sibaprasad Maity Mohtadin Hashemi Yuri L. Lyubchenko
author_facet	Sibaprasad Maity Mohtadin Hashemi Yuri L. Lyubchenko
author_sort	Sibaprasad Maity
title	Nano-assembly of amyloid β peptide: role of the hairpin fold
title_short	Nano-assembly of amyloid β peptide: role of the hairpin fold
title_full	Nano-assembly of amyloid β peptide: role of the hairpin fold
title_fullStr	Nano-assembly of amyloid β peptide: role of the hairpin fold
title_full_unstemmed	Nano-assembly of amyloid β peptide: role of the hairpin fold
title_sort	nano-assembly of amyloid β peptide: role of the hairpin fold
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/27bd31e827a34c1190ad6b96672f031f
work_keys_str_mv	AT sibaprasadmaity nanoassemblyofamyloidbpeptideroleofthehairpinfold AT mohtadinhashemi nanoassemblyofamyloidbpeptideroleofthehairpinfold AT yurillyubchenko nanoassemblyofamyloidbpeptideroleofthehairpinfold
_version_	1718384705804435456

Nano-assembly of amyloid β peptide: role of the hairpin fold

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