Nano-Assembly of amyloid β peptide: Role of the hairpin fold

Sibaprasad Maity, Mohtadin Hashemi, Yuri L Lyubchenko

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article number2344
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Amyloid
Peptides
Molecular Dynamics Simulation

ASJC Scopus subject areas

  • General

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Nano-Assembly of amyloid β peptide : Role of the hairpin fold. / Maity, Sibaprasad; Hashemi, Mohtadin; Lyubchenko, Yuri L.

In: Scientific reports, Vol. 7, No. 1, 2344, 01.12.2017.

Research output: Contribution to journalArticle

Maity, Sibaprasad ; Hashemi, Mohtadin ; Lyubchenko, Yuri L. / Nano-Assembly of amyloid β peptide : Role of the hairpin fold. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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