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Microbial Cell Factories Dec 2012An increasing number of proteins are being shown to assemble into amyloid structures, self-seeding fibrillar aggregates that may lead to pathological states or play...
An increasing number of proteins are being shown to assemble into amyloid structures, self-seeding fibrillar aggregates that may lead to pathological states or play essential biological functions in organisms. Bacterial cell factories have raised as privileged model systems to understand the mechanisms behind amyloid assembly and the cellular fitness cost associated to the formation of these aggregates. In the near future, these bacterial systems will allow implementing high-throughput screening approaches to identify effective modulators of amyloid aggregation.
Topics: Amyloid; Bacteria; Benzothiazoles; Inclusion Bodies; Microscopy, Fluorescence; Models, Biological; Prions; Thiazoles
PubMed: 23272903
DOI: 10.1186/1475-2859-11-166 -
Methods in Molecular Biology (Clifton,... 2012Many bacteria can assemble functional amyloid fibers on their cell surface. The majority of bacterial amyloids contribute to biofilm or other community behaviors where...
Many bacteria can assemble functional amyloid fibers on their cell surface. The majority of bacterial amyloids contribute to biofilm or other community behaviors where cells interact with a surface or with another cell. Bacterial amyloids, like all functional amyloids, share structural and biochemical properties with disease-associated eukaryotic amyloids. The general ability of amyloids to bind amyloid-specific dyes, such as Congo red, and their resistance to denaturation have provided useful tools for scoring and quantifying bacterial amyloid formation. Here, we present basic approaches to study bacterial amyloids by focusing on the well-studied curli amyloid fibers expressed by Enterobacteriaceae. These methods exploit the specific tinctorial and biophysical properties of amyloids. The methods described here are straightforward and can be easily applied by any modern molecular biology lab for the study of other bacterial amyloids.
Topics: Amyloid; Blotting, Western; Congo Red; Escherichia coli; Escherichia coli Proteins; Formates; Mutation; Propanols; Protein Multimerization; Protein Structure, Secondary; Protein Structure, Tertiary
PubMed: 22528099
DOI: 10.1007/978-1-61779-551-0_21 -
Biomolecules Sep 2017Amyloids were first identified in association with amyloidoses, human diseases in which proteins and peptides misfold into amyloid fibrils. Subsequent studies have... (Review)
Review
Amyloids were first identified in association with amyloidoses, human diseases in which proteins and peptides misfold into amyloid fibrils. Subsequent studies have identified an array of functional amyloid fibrils that perform physiological roles in humans. Given the potential for the production of toxic species in amyloid assembly reactions, it is remarkable that cells can produce these functional amyloids without suffering any obvious ill effect. Although the precise mechanisms are unclear, there are a number of ways in which amyloid toxicity may be prevented. These include regulating the level of the amyloidogenic peptides and proteins, minimising the production of prefibrillar oligomers in amyloid assembly reactions, sequestrating amyloids within membrane bound organelles, controlling amyloid assembly by other molecules, and disassembling the fibrils under physiological conditions. Crucially, a better understanding of how toxicity is avoided in the production of functional amyloids may provide insights into the prevention of amyloid toxicity in amyloidoses.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Peptides
PubMed: 28937655
DOI: 10.3390/biom7040071 -
Critical Reviews in Biochemistry and... Aug 2022Although first described in the context of disease, cross-β (amyloid) fibrils have also been found as functional entities in all kingdoms of life. However, what are the... (Review)
Review
Although first described in the context of disease, cross-β (amyloid) fibrils have also been found as functional entities in all kingdoms of life. However, what are the specific properties of the cross-β fibril motif that convey biological function, make them especially suited for their particular purpose, and distinguish them from other fibrils found in biology? This review approaches these questions by arguing that cross-β fibrils are highly periodic, stable, and self-templating structures whose formation is accompanied by substantial conformational change that leads to a multimerization of their core and framing sequences. A discussion of each of these properties is followed by selected examples of functional cross-β fibrils that show how function is usually achieved by leveraging many of these properties.
Topics: Amyloid
PubMed: 35997712
DOI: 10.1080/10409238.2022.2113030 -
Current Opinion in Chemical Biology Oct 2021Originally regarded as a disease symptom, amyloids have shown a rich diversity of functions, including biologically beneficial ones. As such, the traditional view of... (Review)
Review
Originally regarded as a disease symptom, amyloids have shown a rich diversity of functions, including biologically beneficial ones. As such, the traditional view of polypeptide aggregation into amyloid-like structures being 'misfolding' should rather be viewed as 'alternative folding.' Various amyloid folds have been recently used to create highly efficient catalysts with specific catalytic efficiencies rivaling those of enzymes. Here we summarize recent developments and applications of catalytic amyloids, derived from both de novo and bioinspired designs, and discuss how progress in the last 2 years reflects on the field as a whole.
Topics: Amyloid; Catalysis; Peptides; Protein Folding
PubMed: 34425319
DOI: 10.1016/j.cbpa.2021.06.010 -
Advanced Science (Weinheim,... Oct 2023Alzheimer's disease (AD) is a leading form of dementia where the presence of extra-neuronal plaques of Amyloid-β (Aβ) is a pathological hallmark. However, Aβ peptide...
Alzheimer's disease (AD) is a leading form of dementia where the presence of extra-neuronal plaques of Amyloid-β (Aβ) is a pathological hallmark. However, Aβ peptide is also observed in the intestinal tissues of AD patients and animal models. In this study, it is reported that Aβ monomers can target and disintegrate microbial amyloids of FapC and CsgA formed by opportunistic gut pathogens, Pseudomonas aeruginosa and Escherichia coli, explaining a potential role of Aβ in the gut-brain axis. Employing a zebrafish-based transparent in vivo system and whole-mount live-imaging, Aβ is observed to diffuse into the vasculature and subsequently localize with FapC or CsgA fibrils that were injected into the tail muscles of the fish. FapC aggregates, produced after Aβ treatment (Faβ), present selective toxicity to SH-SY5Y neuronal cells while the intestinal Caco-2 cells are shown to phagocytose Faβ in a non-toxic cellular process. After remodeling by Aβ, microbial fibrils lose their native function of cell adhesion with intestinal Caco-2 cells and Aβ dissolves and detaches the microbial fibrils already attached to the cell membrane. Taken together, this study strongly indicates an anti-biofilm role for Aβ monomers that can help aid in the future development of selective anti-Alzheimer's and anti-infective medicine.
Topics: Animals; Humans; Alzheimer Disease; Caco-2 Cells; Zebrafish; Neuroblastoma; Amyloid beta-Peptides; Amyloid; Escherichia coli; Biofilms
PubMed: 37594661
DOI: 10.1002/advs.202301423 -
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 -
Biochimica Et Biophysica Acta Aug 2014Many bacteria assemble extracellular amyloid fibers on their cell surface. Secretion of proteins across membranes and the assembly of complex macromolecular structures... (Review)
Review
Many bacteria assemble extracellular amyloid fibers on their cell surface. Secretion of proteins across membranes and the assembly of complex macromolecular structures must be highly coordinated to avoid the accumulation of potentially toxic intracellular protein aggregates. Extracellular amyloid fiber assembly poses an even greater threat to cellular health due to the highly aggregative nature of amyloids and the inherent toxicity of amyloid assembly intermediates. Therefore, temporal and spatial control of amyloid protein secretion is paramount. The biogenesis and assembly of the extracellular bacterial amyloid curli is an ideal system for studying how bacteria cope with the many challenges of controlled and ordered amyloid assembly. Here, we review the recent progress in the curli field that has made curli biogenesis one of the best-understood functional amyloid assembly pathways. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.
Topics: Amyloid; Amyloidogenic Proteins; Bacterial Proteins; Biofilms; Escherichia coli; Humans; Protein Folding; Protein Transport
PubMed: 24080089
DOI: 10.1016/j.bbamcr.2013.09.010 -
Molecular Neurodegeneration Aug 2022The Amyloid theory of Alzheimer's disease (AD) suggests that the deposition of Amyloid β (Aβ) in the brain triggers a chain of events, involving the deposition of... (Review)
Review
BACKGROUND
The Amyloid theory of Alzheimer's disease (AD) suggests that the deposition of Amyloid β (Aβ) in the brain triggers a chain of events, involving the deposition of phosphorylated Tau and other misfolded proteins, leading to neurodegeneration via neuroinflammation, oxidative stress, and neurovascular factors. The infectious theory linked various infectious agents with the development of AD, raising the possibility that they serve as etiological causes of the disease. Are these theories mutually exclusive, or do they coincide?
MAIN BODY
In this review, we will discuss how the two theories converge. We present a model by which (1) the systemic infectious burden accelerates the development of AD brain pathology via bacterial Amyloids and other pathogen-associated molecular patterns (PAMPs), and (2) the developing AD brain pathology increases its susceptibility to the neurotoxicity of infectious agents -derived PAMPs, which drive neurodegeneration via activated microglia.
CONCLUSIONS
The reciprocal effects of amyloid deposition and systemic infectious burden may lead to a vicious cycle fueling Alzheimer's disease pathogenesis.
Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Brain; Humans; Pathogen-Associated Molecular Pattern Molecules
PubMed: 35986296
DOI: 10.1186/s13024-022-00559-3 -
International Journal of Molecular... May 2022Amyloids are protein aggregates with a specific filamentous structure that are related to a number of human diseases, and also to some important physiological processes... (Review)
Review
Amyloids are protein aggregates with a specific filamentous structure that are related to a number of human diseases, and also to some important physiological processes in animals and other kingdoms of life. Amyloids in yeast can stably propagate as heritable units, prions. Yeast prions are of interest both on their own and as a model for amyloids and prions in general. In this review, we consider the structure of yeast prions and its variation, how such structures determine the balance of aggregated and soluble prion protein through interaction with chaperones and how the aggregated state affects the non-prion functions of these proteins.
Topics: Amyloid; Molecular Chaperones; Prions; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35628548
DOI: 10.3390/ijms23105738