Peptide-Induced Amyloid-Like Conformational Transitions in Proteins

Егоров, Владимир В.; Грудинина, Н. А.; Васин, А. В.; Лебедев, Д. В.

doi:10.1155/2015/723186

Cited by 7 publications

(6 citation statements)

References 36 publications

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“…These flexible fragments in proteins can alter their structure depending on temperature, pH, phosphorylation, and other environmental factors. These conformation changes are shown to be responsible for more than 70 human diseases associated with fibril formation, the most common conformational diseases being amyloidoses, like Alzheimer's disease (AD) and Parkinson's disease (PD) (Egorov et al, 2015). Many of these diseases are neurological disorders, occurring because of conformational changes/misfolding/aggregation of proteins in the brain (Knowles et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

On the Conformational Dynamics of β-Amyloid Forming Peptides: A Computational Perspective

Saravanan

Zhang

et al. 2020

Front. Bioeng. Biotechnol.

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Understanding the conformational dynamics of proteins and peptides involved in important functions is still a difficult task in computational structural biology. Because such conformational transitions in β-amyloid (Aβ) forming peptides play a crucial role in many neurological disorders, researchers from different scientific fields have been trying to address issues related to the folding of Aβ forming peptides together. Many theoretical models have been proposed in the recent years for studying Aβ peptides using mathematical, physicochemical, and molecular dynamics simulation, and machine learning approaches. In this article, we have comprehensively reviewed the developmental advances in the theoretical models for Aβ peptide folding and interactions, particularly in the context of neurological disorders. Furthermore, we have extensively reviewed the advances in molecular dynamics simulation as a tool used for studying the conversions between polymorphic amyloid forms and applications of using machine learning approaches in predicting Aβ peptides and aggregation-prone regions in proteins. We have also provided details on the theoretical advances in the study of Aβ peptides, which would enhance our understanding of these peptides at the molecular level and eventually lead to the development of targeted therapies for certain acute neurological disorders such as Alzheimer's disease in the future.

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Section: Introductionmentioning

confidence: 99%

On the Conformational Dynamics of β-Amyloid Forming Peptides: A Computational Perspective

Saravanan

Zhang

et al. 2020

Front. Bioeng. Biotechnol.

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“…The possibility of conformational transition induction in proteins, when interacting with peptides, is discussed in a review [26]. We considered, earlier, the hypothesis about these mechanisms as they relate to the interaction between the PB1(6-13) peptide and the PB1 subunit N-terminal region (6 th to 25 th residues) [14].…”

Section: Discussionmentioning

confidence: 99%

The amyloidogenicity of the influenza virus PB1-derived peptide sheds light on its antiviral activity

Zabrodskaya

Лебедев

Egorova

et al. 2018

Biophysical Chemistry

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The influenza virus polymerase complex is a promising target for new antiviral drug development. It is known that, within the influenza virus polymerase complex, the PB1 subunit region from the 1st to the 25th amino acid residues has to be is in an alpha-helical conformation for proper interaction with the PA subunit. We have previously shown that PB1(6-13) peptide at low concentrations is able to interact with the PB1 subunit N-terminal region in a peptide model which shows aggregate formation and antiviral activity in cell cultures. In this paper, it was shown that PB1(6-13) peptide is prone to form the amyloid-like fibrillar aggregates. The peptide homo-oligomerization kinetics were examined, and the affinity and characteristic interaction time of PB1(6-13) peptide monomers and the influenza virus polymerase complex PB1 subunit N-terminal region were evaluated by the SPR and TR-SAXS methods. Based on the data obtained, a hypothesis about the PB1(6-13) peptide mechanism of action was proposed: the peptide in its monomeric form is capable of altering the conformation of the PB1 subunit N-terminal region, causing a change from an alpha helix to a beta structure. This conformational change disrupts PB1 and PA subunit interaction and, by that mechanism, the peptide displays antiviral activity.

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“…Indeed, viral proteins tend to form amyloid-like fibrils [2], and at the same time, they often have low homology with human proteins. For most proteins, the induction of a conformational transition by peptides is a process that depends on the coincidence of the primary structure of the protein and the peptide acting on it [3], [4]. Together with the ability to amyloid chain reaction, this suggests that such peptides will be effective at low concentrations and, at the same time, will not affect host proteins.…”

Section: Introductionmentioning

confidence: 99%

Peptide from NSP7 is able to form amyloid-like fibrils: artifact or challenge to drug design?

Garmay

Rubel

Егоров

2022

Preprint

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Using a set of programs for analyzing the primary structure of amyloidogenic proteins, we analyzed the primary structure of the of the COVID-19 NSP7 protein. Peptides containing potential amyloidogenic determinants in the primary structure have been synthesized and shown to be capable of forming amyloid-like fibrils in vitro. In the future, this peptide can be used as a basis for creating antiviral agents that act directly on the spatial structure of the NSP7 subunit of the COVID-19 polymerase.

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Peptide-Induced Amyloid-Like Conformational Transitions in Proteins

Cited by 7 publications

References 36 publications

On the Conformational Dynamics of β-Amyloid Forming Peptides: A Computational Perspective

On the Conformational Dynamics of β-Amyloid Forming Peptides: A Computational Perspective

The amyloidogenicity of the influenza virus PB1-derived peptide sheds light on its antiviral activity

Peptide from NSP7 is able to form amyloid-like fibrils: artifact or challenge to drug design?

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