Protein Self-Assembly at the Liquid–Surface Interface. Surface-Mediated Aggregation Catalysis

Lyubchenko, Yuri L.

doi:10.1021/acs.jpcb.2c09029

Cited by 4 publications

(2 citation statements)

References 119 publications

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“…The overall conclusion of these recent studies is that the phospholipid bilayer works as a catalyst enabling amyloid aggregates to assemble on the surface at physiologically relevant concentrations of Ab, which leads to the model for the formation of the diseaseprone amyloid aggregates schematically shown in Figure 1 (40,53,57,58).…”

Section: Discussionmentioning

confidence: 99%

“…Model for the self-assembly of amyloid aggregates on the membrane surface. (40,53,57,58) According to this model, the interaction of Ab protein with the membrane (step 1) leads to a conformational change of the peptide leading to the formation of the aggregation-prone conformation of the peptide (step 2, misfolding). Interaction of this monomer with another monomer from the solution leads to the formation of the dimer, followed by the growing aggregates (step 3).…”

Section: Discussionmentioning

confidence: 99%

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Amyloid cascade hypothesis for Alzheimer’s disease. Does it work under physiological conditions?

Lyubchenko

2023

Precision Nanomedicine

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<img src=” https://s3.amazonaws.com/production.scholastica/article/77826/large/prnano_942023_toc_figure.jpg?1686262046”> Plaques in the brain consisting of proteins are a hallmark of diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such aggregates can be assembled spontaneously by specialized proteins such as amyloid beta (A β) proteins in the case of AD. Numerous in vitro studies made a foundation for the Amyloid Cascade Hypothesis (ACH), according to which the misfolding of proteins leads to their self-assembly into toxic oligomers along with the formation of amyloid fibrils assembled as plaques in the brain. Notably physiological concentration of A β proteins in the brain is in the low nanomolar concentration, so no spontaneous aggregation of A β protein occurs at such conditions, questioning the validity of the ACH model. However, recent studies revealed that surfaces could play a role as a catalyst of the aggregation process, so self-assembly of A β can be observed at physiologically low concentrations of A β proteins, although no spontaneous aggregation occurs in the bulk solution. The catalytic property of membrane surfaces towards A β aggregation depends on the membrane composition. This finding suggests a number of novel ideas on molecular mechanisms of amyloid self-assembly, which lay a foundation for the development of treatments and preventions for AD, as discussed in this article.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Amyloid cascade hypothesis for Alzheimer’s disease. Does it work under physiological conditions?

Lyubchenko

2023

Precision Nanomedicine

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Insights into the Assembly of Peptides Catalyzed by Polysaccharides

Li,

Zhou,

Zhang

et al. 2024

J. Phys. Chem. B

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Nucleation is a critical step that determines the assembly pathway and the structure and functions of the peptide assemblies. However, the dynamic evolution of interactions between nucleating agents and peptides, as well as between peptides themselves during the nucleation process, remains elusive. Herein, we show that the heterogeneous nucleating agent carboxymethylcellulose (CMC) can promote the nucleation of Aβ 16−20 (KF) peptide. The Forster resonance energy transfer (FRET) technology was used to unveil the interaction dynamics between the CMC and KF peptide. Initially, CMC enriches KF monomers through weak nondirectional electrostatic interactions. The electrostatic screening reduces the electrostatic repulsion between KF molecules. Subsequently, KF−KF interactions become dominant, leading to the dissociation of KF from the CMC and nucleation. By adjustment of the adding time, dosage, size, and active sites of CMC, the assembly kinetics of KF can be effectively controlled. This study helps gain a deep understanding of the early heterogeneous nucleation process of peptide assembly and provides valuable guidance for the rational design of efficient nucleating agents for peptide assembly toward functional materials.

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Preferential Binding of Cations Modulates Electrostatically Driven Protein Aggregation and Disaggregation

Singla,

Bhattacharya

2024

J. Phys. Chem. B

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Protein aggregation resulting in either ordered amyloids or amorphous aggregates is not only restricted to deadly human diseases but also associated with biotechnological challenges encountered in the therapeutic and food industries. Elucidating the key structural determinants of protein aggregation is important to devise targeted inhibitory strategies, but it still remains a formidable task owing to the underlying hierarchy, stochasticity, and complexity associated with the self-assembly processes. Additionally, alterations in solution pH, salt types, and ionic strength modulate various noncovalent interactions, thus affecting the protein aggregation propensity and the aggregation kinetics. However, the molecular origin and a detailed understanding of the effects of weakly and strongly hydrated salts on protein aggregation and their plausible roles in the dissolution of aggregates remain elusive. In this study, using fluorescence and circular dichroism spectroscopy in combination with electron microscopy and light scattering techniques, we show that the ionic size, valency, and extent of hydration of cations play a crucial role in regulating the protein aggregation and disaggregation processes, which may elicit unique methods for governing the balance between protein self-assembly and disassembly.

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Protein Self-Assembly at the Liquid–Surface Interface. Surface-Mediated Aggregation Catalysis

Cited by 4 publications

References 119 publications

Amyloid cascade hypothesis for Alzheimer’s disease. Does it work under physiological conditions?

Amyloid cascade hypothesis for Alzheimer’s disease. Does it work under physiological conditions?

Insights into the Assembly of Peptides Catalyzed by Polysaccharides

Preferential Binding of Cations Modulates Electrostatically Driven Protein Aggregation and Disaggregation

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