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Applied Microbiology and Biotechnology Dec 2022Microbe (including bacteria, fungi, and virus) infection in brains is associated with amyloid fibril deposit and neurodegeneration. Increasing findings suggest that... (Review)
Review
Microbe (including bacteria, fungi, and virus) infection in brains is associated with amyloid fibril deposit and neurodegeneration. Increasing findings suggest that amyloid proteins, like Abeta (Aβ), are important innate immune effectors in preventing infections. In some previous studies, amyloid peptides have been linked to antimicrobial peptides due to their common mechanisms in membrane-disruption ability, while the other mechanisms of bactericidal protein aggregation and protein function knockdown are less discussed. Besides, another important function of amyloid peptides in pathogen agglutination is rarely illustrated. In this review, we summarized and divided the different roles and mechanisms of amyloid peptides against microbes in antimicrobial activity and microbe agglutination activity. Besides, the range of amyloids' antimicrobial spectrum, the effectiveness of amyloid peptide states (monomers, oligomers, and fibrils), and cytotoxicity are discussed. The good properties of amyloid peptides against microbes might provide implications for the development of novel antimicrobial drug. KEY POINTS: • Antimicrobial and/or microbial agglutination is a characteristic of amyloid peptides. • Various mechanisms of amyloid peptides against microbes are discovered recently. • Amyloid peptides might be developed into novel antimicrobial drugs.
Topics: Amyloid; Amyloid beta-Peptides; Anti-Infective Agents; Amyloidogenic Proteins; Anti-Bacterial Agents; Agglutination
PubMed: 36322251
DOI: 10.1007/s00253-022-12246-w -
Microbial Physiology 2021Amyloids have proven to be a widespread phenomenon rather than an exception. Many proteins presenting the hallmarks of this characteristic beta sheet-rich folding have... (Review)
Review
Amyloids have proven to be a widespread phenomenon rather than an exception. Many proteins presenting the hallmarks of this characteristic beta sheet-rich folding have been described to date. Particularly common are functional amyloids that play an important role in the promotion of survival and pathogenicity in prokaryotes. Here, we describe important developments in amyloid protein research that relate to microbe-microbe and microbe-host interactions in the plant microbiome. Starting with biofilms, which are a broad strategy for bacterial persistence that is extremely important for plant colonization. Microbes rely on amyloid-based mechanisms to adhere and create a protective coating that shelters them from external stresses and promotes cooperation. Another strategy generally carried out by amyloids is the formation of hydrophobic surface layers. Known as hydrophobins, these proteins coat the aerial hyphae and spores of plant pathogenic fungi, as well as certain bacterial biofilms. They contribute to plant virulence through promoting dissemination and infectivity. Furthermore, antimicrobial activity is an interesting outcome of the amyloid structure that has potential application in medicine and agriculture. There are many known antimicrobial amyloids released by animals and plants; however, those produced by bacteria or fungi remain still largely unknown. Finally, we discuss amyloid proteins with a more indirect mode of action in their host interactions. These include virulence-promoting harpins, signaling transduction that functions through amyloid templating, and root nodule bacteria proteins that promote plant-microbe symbiosis. In summary, amyloids are an interesting paradigm for their many functional mechanisms linked to bacterial survival in plant-associated microbial communities.
Topics: Amyloid; Amyloidogenic Proteins; Animals; Bacteria; Biofilms; Microbiota
PubMed: 34107493
DOI: 10.1159/000516014 -
Biomolecules Dec 2021Amyloids are filamentous protein aggregates that are associated with a number of incurable diseases, termed amyloidoses. Amyloids can also manifest as infectious or... (Review)
Review
Amyloids are filamentous protein aggregates that are associated with a number of incurable diseases, termed amyloidoses. Amyloids can also manifest as infectious or heritable particles, known as prions. While just one prion is known in humans and animals, more than ten prion amyloids have been discovered in fungi. The propagation of fungal prion amyloids requires the chaperone Hsp104, though in excess it can eliminate some prions. Even though Hsp104 acts to disassemble prion fibrils, at normal levels it fragments them into multiple smaller pieces, which ensures prion propagation and accelerates prion conversion. Animals lack Hsp104, but disaggregation is performed by the same complement of chaperones that assist Hsp104 in yeast-Hsp40, Hsp70, and Hsp110. Exogenous Hsp104 can efficiently cooperate with these chaperones in animals and promotes disaggregation, especially of large amyloid aggregates, which indicates its potential as a treatment for amyloid diseases. However, despite the significant effects, Hsp104 and its potentiated variants may be insufficient to fully dissolve amyloid. In this review, we consider chaperone mechanisms acting to disassemble heritable protein aggregates in yeast and animals, and their potential use in the therapy of human amyloid diseases.
Topics: Amyloid; Animals; Fungal Proteins; Fungi; Heat-Shock Proteins; Humans; Models, Molecular; Prions; Protein Aggregates; Protein Conformation
PubMed: 34944528
DOI: 10.3390/biom11121884 -
Journal of Advanced Research Feb 2022Protein aggregation and deposition of uniformly arranged amyloid fibrils in the form of plaques or amorphous aggregates is characteristic of amyloid diseases. The... (Review)
Review
INTRODUCTION
Protein aggregation and deposition of uniformly arranged amyloid fibrils in the form of plaques or amorphous aggregates is characteristic of amyloid diseases. The accumulation and deposition of proteins result in toxicity and cause deleterious effects on affected individuals known as amyloidosis. There are about fifty different proteins and peptides involved in amyloidosis including neurodegenerative diseases and diseases affecting vital organs. Despite the strenuous effort to find a suitable treatment option for these amyloid disorders, very few compounds had made it to unsuccessful clinical trials. It has become a compelling challenge to understand and manage amyloidosis with the increased life expectancy and ageing population.
OBJECTIVE
While most of the currently available literature and knowledge base focus on the amyloid inhibitory mechanism as a treatment option, it is equally important to organize and understand amyloid disaggregation strategies. Disaggregation strategies are important and crucial as they are present innately functional in many living systems and dissolution of preformed amyloids may provide a direct benefit in many pathological conditions. In this review, we have compiled the known amyloid disaggregation mechanism, interactions, and possibilities of using disaggregases as a treatment option for amyloidosis.
METHODS
We have provided the structural details using protein-ligand docking models to visualize the interaction between these disaggregases with amyloid fibrils and their respective proposed amyloid disaggregation mechanisms.
RESULTS
After reviewing and comparing the different amyloid disaggregase systems and their proposed mechanisms, we presented two different hypotheses for ATP independent disaggregases using L-PGDS as a model.
CONCLUSION
Finally, we have highlighted the importance of understanding the underlying disaggregation mechanisms used by these chaperones and organic compounds before the implementation of these disaggregases as a potential treatment option for amyloidosis.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Molecular Chaperones; Protein Aggregates
PubMed: 35127169
DOI: 10.1016/j.jare.2021.05.007 -
Chemical Reviews Jul 2021This review will focus on the process of amyloid-type protein aggregation. Amyloid fibrils are an important hallmark of protein misfolding diseases and therefore have... (Review)
Review
This review will focus on the process of amyloid-type protein aggregation. Amyloid fibrils are an important hallmark of protein misfolding diseases and therefore have been investigated for decades. Only recently, however, atomic or near-atomic resolution structures have been elucidated from various in vitro and ex vivo obtained fibrils. In parallel, the process of fibril formation has been studied in vitro under highly artificial but comparatively reproducible conditions. The review starts with a summary of what is known and speculated from artificial in vitro amyloid-type protein aggregation experiments. A partially hypothetic fibril selection model will be described that may be suitable to explain why amyloid fibrils look the way they do, in particular, why at least all so far reported high resolution cryo-electron microscopy obtained fibril structures are in register, parallel, cross-β-sheet fibrils that mostly consist of two protofilaments twisted around each other. An intrinsic feature of the model is the prion-like nature of all amyloid assemblies. Transferring the model from the in vitro point of view to the in vivo situation is not straightforward, highly hypothetic, and leaves many open questions that need to be addressed in the future.
Topics: Amyloid; Amyloidogenic Proteins; Animals; Cryoelectron Microscopy; Humans; Prions; Protein Aggregates
PubMed: 34137605
DOI: 10.1021/acs.chemrev.1c00196 -
The FEBS Journal Apr 2022Amyloid aggregation results from the self-assembly of identical aggregation-prone sequences into cross-beta-sheet structures. The process is best known for its... (Review)
Review
Amyloid aggregation results from the self-assembly of identical aggregation-prone sequences into cross-beta-sheet structures. The process is best known for its association with a wide range of human pathologies but also as a functional mechanism in all kingdoms of life. Less well elucidated is the role of heterotypic interactions between amyloids and other proteins and macromolecules and how this contributes to disease. We here review current data with a focus on neurodegenerative amyloid-associated diseases. Evidence indicates that heterotypic interactions occur in a wide range of amyloid processes and that these interactions modify fundamental aspects of amyloid aggregation including seeding, aggregation rates and toxicity. More work is required to understand the mechanistic origin of these interactions, but current understanding suggests that both supersaturation and sequence-specific binding can contribute to heterotypic amyloid interactions. Further unravelling these mechanisms may help to answer outstanding questions in the field including the selective vulnerability of cells types and tissues and the stereotypical spreading patterns of amyloids in disease.
Topics: Amyloid; Amyloid beta-Peptides; Amyloidogenic Proteins; Amyloidosis; Humans; Neurodegenerative Diseases
PubMed: 33460517
DOI: 10.1111/febs.15719 -
Chemical Reviews Dec 2019Amyloids are a broad class of proteins and peptides that can misfold and assemble into long unbranched fibrils with a cross-β conformation. These misfolding and... (Review)
Review
Amyloids are a broad class of proteins and peptides that can misfold and assemble into long unbranched fibrils with a cross-β conformation. These misfolding and aggregation events are associated with the onset of a variety of human diseases, among them, Alzheimer's disease, Parkinson's disease, and Huntington disease. Our understanding of amyloids has been greatly supported by fluorescent molecular probes, such as thioflavin-T, which shows an increase in fluorescence emission upon binding to fibrillar aggregates. Since the first application of thioflavin-T in amyloid studies nearly 30 years ago, many probes have emerged exhibiting a variety of responses to amyloids, such as intensity changes, shifts in fluorescence maxima, and variations in lifetimes, among many others. These probes have shed light on a variety of topics including the kinetics of amyloid aggregation, the effectiveness of amyloid aggregation inhibitors, the elucidation of binding sites in amyloid structures, and the staining of amyloids aggregates in vitro, ex vivo, and in vivo. In this Review, we discuss the design, properties, and application of photoactive probes used to study amyloid aggregation, as well as the challenges faced by current probes and techniques, and the novel approaches that are emerging to address these challenges.
Topics: Amyloid beta-Peptides; Amyloidogenic Proteins; Animals; Benzothiazoles; Binding Sites; Fluorescent Dyes; Humans; Models, Molecular; Peptide Fragments; Protein Aggregates; Protein Aggregation, Pathological; Spectrometry, Fluorescence
PubMed: 31675223
DOI: 10.1021/acs.chemrev.9b00404 -
Journal of Molecular Biology Oct 2021Protein aggregation is a widespread phenomenon with important implications in many scientific areas. Although amyloid formation is typically considered as detrimental,... (Review)
Review
Protein aggregation is a widespread phenomenon with important implications in many scientific areas. Although amyloid formation is typically considered as detrimental, functional amyloids that perform physiological roles have been identified in all kingdoms of life. Despite their functional and pathological relevance, the structural details of the majority of molecular species involved in the amyloidogenic process remains elusive. Here, we explore the application of AlphaFold, a highly accurate protein structure predictor, in the field of protein aggregation. While we envision a straightforward application of AlphaFold in assisting the design of globular proteins with improved solubility for biomedical and industrial purposes, the use of this algorithm for predicting the structure of aggregated species seems far from trivial. First, in amyloid diseases, the presence of multiple amyloid polymorphs and the heterogeneity of aggregation intermediates challenges the "one sequence, one structure" paradigm, inherent to sequence-based predictions. Second, aberrant aggregation is not the subject of positive selective pressure, precluding the use of evolutionary-based approaches, which are the core of the AlphaFold pipeline. Instead, amyloid polymorphism seems to be constrained by the need for a defined structure-activity relationship in functional amyloids. They may thus provide a starting point for the application of AlphaFold in the amyloid landscape.
Topics: Amyloid; Amyloidosis; Animals; Humans; Models, Molecular; Protein Aggregates; Protein Aggregation, Pathological; Protein Conformation; Protein Folding; Software
PubMed: 34023402
DOI: 10.1016/j.jmb.2021.167059 -
Biochemistry. Biokhimiia May 2022Amyloids are protein aggregates with the cross-β structure. The interest in amyloids is explained, on the one hand, by their role in the development of socially... (Review)
Review
Amyloids are protein aggregates with the cross-β structure. The interest in amyloids is explained, on the one hand, by their role in the development of socially significant human neurodegenerative diseases, and on the other hand, by the discovery of functional amyloids, whose formation is an integral part of cellular processes. To date, more than a hundred proteins with the amyloid or amyloid-like properties have been identified. Studying the structure of amyloid aggregates has revealed a wide variety of protein conformations. In the review, we discuss the diversity of protein folds in the amyloid-like aggregates and the characteristic features of amyloid aggregates that determine their unusual properties, including stability and interaction with amyloid-specific dyes. The review also describes the diversity of amyloid aggregates and its significance for living organisms.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Polymorphism, Genetic; Protein Conformation
PubMed: 35790379
DOI: 10.1134/S0006297922050066 -
Current Opinion in Structural Biology Feb 2022The number of atomic-resolution structures of disease-associated amyloids has greatly increased in recent years. These structures have confirmed not only the polymorphic... (Review)
Review
The number of atomic-resolution structures of disease-associated amyloids has greatly increased in recent years. These structures have confirmed not only the polymorphic nature of amyloids but also the association of specific polymorphs to particular proteinopathies. These observations are strengthening the view that amyloid polymorphism is a marker for specific pathological subtypes (e.g. in tauopathies or synucleinopathies). The nature of this association and how it relates to the selective cellular vulnerability of amyloid nucleation, propagation and toxicity are still unclear. Here, we provide an overview of the mechanistic insights provided by recent patient-derived amyloid structures. We discuss the framework organisation of amyloid polymorphism and how heterotypic amyloid interactions with the physiological environment could modify the solubility and assembly of amyloidogenic proteins. We conclude by hypothesising how such interactions could contribute to selective cellular vulnerability.
Topics: Amyloid; Amyloidogenic Proteins; Humans
PubMed: 34942566
DOI: 10.1016/j.sbi.2021.11.007