Nanodisc-Forming Scaffold Protein Promoted Retardation of Amyloid-Beta Aggregation

Journal of Molecular Biology
Bikash SahooAyyalusamy Ramamoorthy

Abstract

Peptidic nanodiscs are useful membrane mimetic tools for structural and functional studies of membrane proteins, and membrane interacting peptides including amyloids. Here, we demonstrate anti-amyloidogenic activities of a nanodisc-forming 18-residue peptide (denoted as 4F), both in lipid-bound and lipid-free states by using Alzheimer's amyloid-beta (Aβ40) peptide as an example. Fluorescence-based amyloid fibrillation kinetic assays showed a significant delay in Aβ40 amyloid aggregation by the 4F peptide. In addition, 4F-encased lipid nanodiscs, at an optimal concentration of 4F (>20 μM) and nanodisc size (<10 nm), significantly affect amyloid fibrillation. A comparison of experimental results obtained from nanodiscs with that obtained from liposomes revealed a substantial inhibitory efficacy of 4F-lipid nanodiscs against Aβ40 aggregation and were also found to be suitable to trap Aβ40 intermediates. A combination of atomistic molecular dynamics simulations with NMR and circular dichroism experimental results exhibited a substantial change in Aβ40 conformation upon 4F binding through electrostatic and π-π interactions. Specifically, the 4F peptide was found to interfere with the central β-sheet-forming residues of Aβ40 through ...Continue Reading

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Citations

Nov 1, 2018·Chemical Communications : Chem Comm·Bikash R SahooAyyalusamy Ramamoorthy
Apr 18, 2020·Chemical Communications : Chem Comm·Bikash R SahooAyyalusamy Ramamoorthy
Jul 9, 2020·Nanoscale·Nicholas AndrikopoulosPu Chun Ke
Jun 21, 2020·International Journal of Molecular Sciences·Takahiro Watanabe-NakayamaKenjiro Ono
Nov 10, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Suman DasDhermendra K Tiwari
Dec 24, 2019·Journal of Molecular Biology·Bikash Ranjan SahooAyyalusamy Ramamoorthy
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