Membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein

Bandyopadhyay, Arnab; Sannigrahi, Achinta; Chattopadhyay, Krishnananda

doi:10.1039/d0cb00203h

Cited by 8 publications

(5 citation statements)

References 47 publications

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“…A growing number of studies indicate that an interaction between lipid bilayers and amyloid-forming proteins occurs and that lipids play an important role in the kinetics of amyloid assembly or stability [38][39][40][41][42][43]. The lipid membrane may, indeed, provide an interface to increase the protein local concentration, facilitating fibrillization.…”

Section: Discussionmentioning

confidence: 99%

The Amyloid Assembly of the Bacterial Hfq Is Lipid-Driven and Lipid-Specific

Turbant,

Machiels,

Waeytens

et al. 2024

IJMS

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Under specific conditions, some proteins can self-assemble into fibrillar structures called amyloids. Initially, these proteins were associated with neurodegenerative diseases in eucaryotes. Nevertheless, they have now been identified in the three domains of life. In bacteria, they are involved in diverse biological processes and are usually useful for the cell. For this reason, they are classified as “functional amyloids”. In this work, we focus our analysis on a bacterial functional amyloid called Hfq. Hfq is a pleiotropic regulator that mediates several aspects of genetic expression, mainly via the use of small noncoding RNAs. Our previous work showed that Hfq amyloid-fibrils interact with membranes. This interaction influences Hfq amyloid structure formation and stability, but the specifics of the lipid on the dynamics of this process is unknown. Here, we show, using spectroscopic methods, how lipids specifically drive and modulate Hfq amyloid assembly or, conversely, its disassembly. The reported effects are discussed in light of the consequences for bacterial cell life.

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Section: Discussionmentioning

confidence: 99%

The Amyloid Assembly of the Bacterial Hfq Is Lipid-Driven and Lipid-Specific

Turbant,

Machiels,

Waeytens

et al. 2024

IJMS

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“…[30][31][32] Both the impact of membranes on peptide structure and self-assembly kinetics as well as the action of peptides on membranes have been studied extensively. [33][34][35][36][37][38][39][40][41][42][43] The membrane damage caused by amyloid-forming peptides has been attributed to different oligomeric species as well as the bril growth process. 44,45 Previous work either proposed the disruption of membranes by peptides or the modulation of peptide self-assembly by membranes as the initial process in relation to disease, or considered both processes as concomitant.…”

Section: Introductionmentioning

confidence: 99%

“…30–32 Both the impact of membranes on peptide structure and self-assembly kinetics as well as the action of peptides on membranes have been studied extensively. 33–43…”

Section: Introductionmentioning

confidence: 99%

Lipid oxidation controls peptide self-assembly near membranes through a surface attraction mechanism

et al. 2023

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“…[30][31][32] Both the impact of membranes on peptide structure and self-assembly kinetics as well as the action of peptides on membranes have been studied extensively. 33,34,43,[35][36][37][38][39][40][41][42] The membrane damage caused by amyloidogenic peptides has been attributed to different oligomeric species as well as the fibril growth process. 44,45 Previous work either proposed the disruption of membranes by peptides or the modulation of peptide self-assembly by membranes as the initial process in relation to disease, or considered both processes as concomitant.…”

Section: Introductionmentioning

confidence: 99%

Lipid Oxidation Controls Peptide Self-Assembly near Membranes

John

Piantavigna

Dealey

et al. 2022

Preprint

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The self-assembly of peptides into supramolecular fibril structures has been linked to neurodegenerative diseases such as Alzheimer's disease but has also been observed in functional roles. Peptides are physiologically exposed to crowded environments of biomacromolecules, and particularly membrane lipids, within a cellular milieu. Previous research has shown that membranes can both accelerate and inhibit peptide self-assembly. Here, we studied the impact of biomimetic membranes that mimic cellular oxidative stress and compared this to mammalian and bacterial membranes. Using molecular dynamics simulations and experiments, we propose a model that explains how changes in peptide-membrane binding, electrostatics, and peptide secondary structure stabilization determine the nature of peptide self-assembly. We explored the influence of zwitterionic (POPC), anionic (POPG) and oxidized (PazePC) phospholipids, as well as cholesterol, and mixtures thereof, on the self-assembly kinetics of the amyloid β (1–40) peptide (Aβ40), linked to Alzheimer's disease, and the amyloid-forming antimicrobial peptide uperin 3.5 (U3.5). We show that the presence of an oxidized lipid had similar effects on peptide self-assembly as the bacterial mimetic membrane. While Aβ40 fibril formation was accelerated, U3.5 aggregation was inhibited by the same lipids at the same peptide-to-lipid ratio. We attribute these findings and peptide-specific effects to differences in peptide-membrane adsorption with U3.5 being more strongly bound to the membrane surface and stabilized in an α-helical conformation compared to Aβ40. Different peptide-to-lipid ratios resulted in different effects. Molecular dynamics simulations provided detailed mechanistic insights into the peptide-lipid interactions and secondary structure stability. We found that electrostatic interactions are a primary driving force for peptide-membrane interaction, enabling us to propose a model for predictions how cellular changes might impact peptide self-assembly in vivo, and potentially impact related diseases.

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Membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein

Abstract: This study provides a mechanistic description of how the membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein.

Cited by 8 publications

References 47 publications

The Amyloid Assembly of the Bacterial Hfq Is Lipid-Driven and Lipid-Specific

The Amyloid Assembly of the Bacterial Hfq Is Lipid-Driven and Lipid-Specific

Lipid oxidation controls peptide self-assembly near membranes through a surface attraction mechanism

Lipid Oxidation Controls Peptide Self-Assembly near Membranes

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