Structure and Polymorphism of Amyloid and Amyloid-Like Aggregates

Matiiv, Anton B.; Trubitsina, Nina P.; Matveenko, Andrew G.; Barbitoff, Yury A.; Zhouravleva, Galina A.; Bondarev, Stanislav A.

doi:10.1134/s0006297922050066

Cited by 5 publications

(3 citation statements)

References 136 publications

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“…Nowadays, a large number of amyloids are known among various groups of organisms [6]. Some of these proteins are functional amyloids and are responsible for various biological functions.…”

Section: Discussionmentioning

confidence: 99%

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Identification of New FG-Repeat Nucleoporins with Amyloid Properties

Данилов

Sukhanova

Rogoza

et al. 2023

IJMS

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Amyloids are fibrillar protein aggregates with a cross-β structure. More than two hundred different proteins with amyloid or amyloid-like properties are already known. Functional amyloids with conservative amyloidogenic regions were found in different organisms. Protein aggregation appears to be beneficial for the organism in these cases. Therefore, this property might be conservative for orthologous proteins. The amyloid aggregates of the CPEB protein were suggested to play an important role in the long-term memory formation in Aplysia californica, Drosophila melanogaster, and Mus musculus. Moreover, the FXR1 protein demonstrates amyloid properties among the Vertebrates. A few nucleoporins (e.g., yeast Nup49, Nup100, Nup116, and human Nup153 and Nup58), are supposed or proved to form amyloid fibrils. In this study, we performed wide-scale bioinformatic analysis of nucleoporins with FG-repeats (phenylalanine–glycine repeats). We demonstrated that most of the barrier nucleoporins possess potential amyloidogenic properties. Furthermore, the aggregation-prone properties of several Nsp1 and Nup100 orthologs in bacteria and yeast cells were analyzed. Only two new nucleoporins, Drosophila melanogaster Nup98 and Schizosaccharomyces pombe Nup98, aggregated in different experiments. At the same time, Taeniopygia guttata Nup58 only formed amyloids in bacterial cells. These results rather contradict the hypothesis about the functional aggregation of nucleoporins.

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“…Nowadays, a large number of amyloids are known among various groups of organisms [6]. Some of these proteins are functional amyloids and are responsible for various biological functions.…”

Section: Discussionmentioning

confidence: 99%

“…Amyloids are fibrillar protein aggregates with cross-β structure (for review, see [1][2][3][4][5][6]). Amyloids were discovered as protein deposits associated with different diseases.…”

Section: Introductionmentioning

confidence: 99%

Identification of New FG-Repeat Nucleoporins with Amyloid Properties

Данилов

Sukhanova

Rogoza

et al. 2023

IJMS

Self Cite

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“…An important aspect of yeast biology is the existence of yeast prions—self-perpetuating protein aggregates that confer changes to the yeast’s phenotype and are inherited in a non-Mendelian fashion (for review, see [ 2 ]). Most yeast prion aggregates have amyloid nature, i.e., their prion conformers form long fibrillar structures with a typical regular structure (for review, see [ 3 , 4 , 5 ]).…”

Section: Introductionmentioning

confidence: 99%

Processing of Fluorescent Proteins May Prevent Detection of Prion Particles in [PSI+] Cells

Matveenko

Ryzhkova

Zaytseva

et al. 2022

Biology

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Yeast is a convenient model for studying protein aggregation as it is known to propagate amyloid prions. [PSI+] is the prion form of the release factor eRF3 (Sup35). Aggregated Sup35 causes defects in termination of translation, which results in nonsense suppression in strains carrying premature stop codons. N-terminal and middle (M) domains of Sup35 are necessary and sufficient for maintaining [PSI+] in cells while preserving the prion strain’s properties. For this reason, Sup35NM fused to fluorescent proteins is often used for [PSI+] detection and investigation. However, we found that in such chimeric constructs, not all fluorescent proteins allow the reliable detection of Sup35 aggregates. Particularly, transient overproduction of Sup35NM-mCherry resulted in a diffuse fluorescent pattern in the [PSI+] cells, while no loss of prions and no effect on the Sup35NM prion properties could be observed. This effect was reproduced in various unrelated strain backgrounds and prion variants. In contrast, Sup35NM fused to another red fluorescent protein, TagRFP-T, allowed the detection of [PSI+] aggregates. Analysis of protein lysates showed that Sup35NM-mCherry is actively degraded in the cell. This degradation was not caused by vacuolar proteases and the ubiquitin-proteasomal system implicated in the Sup35 processing. Even though the intensity of this proteolysis was higher than that of Sup35NM-GFP, it was roughly the same as in the case of Sup35NM-TagRFP-T. Thus, it is possible that, in contrast to TagRFP-T, degradation products of Sup35NM-mCherry still preserve their fluorescent properties while losing the ability to decorate pre-existing Sup35 aggregates. This results in diffuse fluorescence despite the presence of the prion aggregates in the cell. Thus, tagging with fluorescent proteins should be used with caution, as such proteolysis may increase the rate of false-negative results when detecting prion-bearing cells.

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Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

Kell,

Pretorius

2024

Preprint

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In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils and fibrils exhibiting a cross-β motif of parallel or antiparallel β-sheets oriented perpendicular to the fibre direction. These protofibrils and fibrils can intertwine to form mature amyloid fibres. Similar phenomena occur in blood from individuals with circulating inflammatory molecules (also those originating from viruses and bacteria). In the presence of inflammagens, pathological clotting can occur, that results in an anomalous amyloid form termed fibrinaloid microclots. Previous proteomic analyses of these microclots have shown the presence of non-fibrin(ogen) proteins, suggesting a more complex mechanism than simple entrapment. We provide evidence against a simple entrapment model, noting that clot pores are too large and centrifugation would have removed weakly bound proteins. Instead, we explore whether co-aggregation into amyloid fibres may involve axial (multiple proteins within the same fibril), lateral (single-protein fibrils contributing to a fibre), or both types of integration. Our analysis of proteomic data from fibrinaloid microclots in different diseases shows no significant overlap with the normal plasma proteome and no correlation between plasma protein abundance and presence in microclots. Notably, abundant plasma proteins like α-2-macroglobulin, fibronectin, and transthyretin are absent from microclots, while less abundant proteins such as adiponectin, periostin, and von Willebrand Factor are well represented. Using bioinformatic tools including AmyloGram and AnuPP, we found that proteins entrapped in fibrinaloid microclots exhibit high amyloidogenic tendencies, suggesting their integration as cross-β elements into amyloid structures. This integration likely contributes to the microclots’ resistance to proteolysis. Our findings underscore the role of cross-seeding in fibrinaloid microclot formation and highlight the need for further investigation into their structural properties and implications in thrombotic and amyloid diseases. These insights provide a foundation for developing novel diagnostic and therapeutic strategies targeting amyloidogenic cross-seeding in blood clotting disorders.

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Structure and Polymorphism of Amyloid and Amyloid-Like Aggregates

Cited by 5 publications

References 136 publications

Identification of New FG-Repeat Nucleoporins with Amyloid Properties

Identification of New FG-Repeat Nucleoporins with Amyloid Properties

Processing of Fluorescent Proteins May Prevent Detection of Prion Particles in [PSI+] Cells

Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

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