Evolutionary Conservation of Systemic and Reversible Amyloid Aggregation

In response to environmental stress, human cells have been shown to form reversible amyloid aggregates within the nucleus, termed amyloid bodies (A-bodies). These protective physiological structures share many of the biophysical characteristics associated with the pathological amyloids found in Alzheimer's and Parkinson's disease. Here, we show that A-bodies are evolutionarily conserved across the eukaryotic domain, with their detection in D. melanogaster and S. cerevisiae marking the first examples of these functional amyloids being induced outside of a cultured cell setting. The conditions triggering amyloidogenesis varied significantly among the species tested, with results indicating that A-body formation is a severe, but sub-lethal, stress response pathway that is tailored to an organism's environmental norms. RNA-sequencing analyses demonstrate that the regulatory low-complexity long non-coding RNAs that drive A-body aggregation are both conserved and essential in human, mouse, and chicken cells. Thus, the identification of these natural and reversible functional amyloids in a variety of evolutionarily diverse species, highlights the physiological significance of this protein conformation and will be informative in advancing our understanding of both functional and pathological amyloid aggregation events.

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“What Doesn’t Kill You Makes You Stronger”: Future Applications of Amyloid Aggregates in Biomedicine

Molecules ◽

10.3390/molecules25225245 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5245

Author(s):

Sherin Abdelrahman ◽

Mawadda Alghrably ◽

Joanna Izabela Lachowicz ◽

Abdul-Hamid Emwas ◽

Charlotte A. E. Hauser ◽

...

Keyword(s):

Protein Aggregation ◽

Biomedical Applications ◽

Amyloid Aggregation ◽

Factors Affecting ◽

Amyloid Peptides ◽

Amyloid Aggregates ◽

Innovative Materials ◽

Functional Amyloids ◽

Innovative Medicine ◽

Aggregation Factors

Amyloid proteins are linked to the pathogenesis of several diseases including Alzheimer’s disease, but at the same time a range of functional amyloids are physiologically important in humans. Although the disease pathogenies have been associated with protein aggregation, the mechanisms and factors that lead to protein aggregation are not completely understood. Paradoxically, unique characteristics of amyloids provide new opportunities for engineering innovative materials with biomedical applications. In this review, we discuss not only outstanding advances in biomedical applications of amyloid peptides, but also the mechanism of amyloid aggregation, factors affecting the process, and core sequences driving the aggregation. We aim with this review to provide a useful manual for those who engineer amyloids for innovative medicine solutions.

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Role of the Structural Characteristics of Dendrimers in the Manifestation of the Antiamyloid Properties

INEOS OPEN ◽

10.32931/io2018r ◽

2020 ◽

Vol 3 ◽

Author(s):

S. A. Sorokina ◽

◽

Yu. Yu. Stroilova ◽

V. I. Muronets ◽

Z. B. Shifrina ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Structural Characteristics ◽

Short Review ◽

External Factors ◽

Amyloid Aggregation ◽

Amyloid Proteins ◽

Molecular Parameters ◽

Amyloid Aggregates ◽

Aggregation Processes

Among the compounds able to efficiently inhibit the amyloid aggregation of proteins and decompose the amyloid aggregates that cause neurodegenerative diseases, of particular interest are dendrimers, which represent individual macromolecules with the hypercrosslinked architectures and given molecular parameters. This short review outlines the peculiarities of the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. The potential of application of dendrimers in further investigations on the aggregation processes of amyloid proteins as the compounds that exhibit the remarkable antiamyloid activity is evaluated.

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Promiscuous Cross-seeding between Bacterial Amyloids Promotes Interspecies Biofilms

Journal of Biological Chemistry ◽

10.1074/jbc.m112.383737 ◽

2012 ◽

Vol 287 (42) ◽

pp. 35092-35103 ◽

Cited By ~ 61

Author(s):

Yizhou Zhou ◽

Daniel Smith ◽

Bryan J. Leong ◽

Kristoffer Brännström ◽

Fredrik Almqvist ◽

...

Keyword(s):

Escherichia Coli ◽

Shewanella Oneidensis ◽

Bacterial Attachment ◽

Surface Attachment ◽

E Coli ◽

Amyloid Aggregates ◽

Functional Amyloids ◽

Biofilm Development ◽

Distant Homolog

Amyloids are highly aggregated proteinaceous fibers historically associated with neurodegenerative conditions including Alzheimers, Parkinsons, and prion-based encephalopathies. Polymerization of amyloidogenic proteins into ordered fibers can be accelerated by preformed amyloid aggregates derived from the same protein in a process called seeding. Seeding of disease-associated amyloids and prions is highly specific and cross-seeding is usually limited or prevented. Here we describe the first study on the cross-seeding potential of bacterial functional amyloids. Curli are produced on the surface of many Gram-negative bacteria where they facilitate surface attachment and biofilm development. Curli fibers are composed of the major subunit CsgA and the nucleator CsgB, which templates CsgA into fibers. Our results showed that curli subunit homologs from Escherichia coli, Salmonella typhimurium LT2, and Citrobacter koseri were able to cross-seed in vitro. The polymerization of Escherichia coli CsgA was also accelerated by fibers derived from a distant homolog in Shewanella oneidensis that shares less than 30% identity in primary sequence. Cross-seeding of curli proteins was also observed in mixed colony biofilms with E. coli and S. typhimurium. CsgA was secreted from E. coli csgB− mutants assembled into fibers on adjacent S. typhimurium that presented CsgB on its surfaces. Similarly, CsgA was secreted by S. typhimurium csgB− mutants formed curli on CsgB-presenting E. coli. This interspecies curli assembly enhanced bacterial attachment to agar surfaces and supported pellicle biofilm formation. Collectively, this work suggests that the seeding specificity among curli homologs is relaxed and that heterogeneous curli fibers can facilitate multispecies biofilm development.

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Evolution of the Yeast Recombination Landscape

Molecular Biology and Evolution ◽

10.1093/molbev/msy233 ◽

2018 ◽

Vol 36 (2) ◽

pp. 412-422 ◽

Cited By ~ 4

Author(s):

Haoxuan Liu ◽

Calum J Maclean ◽

Jianzhi Zhang

Keyword(s):

Recombination Rate ◽

Yeast Species ◽

Evolutionary Conservation ◽

Double Strand Breaks ◽

Strand Breaks ◽

Crossover Interference ◽

Recombination Hotspots ◽

Genomic Landscape ◽

Evolutionarily Conserved ◽

Cold Spots

Abstract Meiotic recombination comprises crossovers and noncrossovers. Recombination, crossover in particular, shuffles mutations and impacts both the level of genetic polymorphism and the speed of adaptation. In many species, the recombination rate varies across the genome with hot and cold spots. The hotspot paradox hypothesis asserts that recombination hotspots are evolutionarily unstable due to self-destruction. However, the genomic landscape of double-strand breaks (DSBs), which initiate recombination, is evolutionarily conserved among divergent yeast species, casting doubt on the hotspot paradox hypothesis. Nonetheless, because only a subset of DSBs are associated with crossovers, the evolutionary conservation of the crossover landscape could differ from that of DSBs. Here, we investigate this possibility by generating a high-resolution recombination map of the budding yeast Saccharomyces paradoxus through whole-genome sequencing of 50 meiotic tetrads and by comparing this recombination map with that of S. cerevisiae. We observe a 40% lower recombination rate in S. paradoxus than in S. cerevisiae. Compared with the DSB landscape, the crossover landscape is even more conserved. Further analyses indicate that the elevated conservation of the crossover landscape is explained by a near-subtelomeric crossover preference in both yeasts, which we find to be attributable at least in part to crossover interference. We conclude that the yeast crossover landscape is highly conserved and that the evolutionary conservation of this landscape can differ from that of the DSB landscape.

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The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure

10.1101/2020.06.05.135673 ◽

2020 ◽

Author(s):

Yunpeng Sun ◽

Kun Zhao ◽

Wencheng Xia ◽

Jinge Gu ◽

Yeyang Ma ◽

...

Keyword(s):

Phase Separation ◽

Nuclear Localization ◽

Amyloid Fibril ◽

Low Complexity ◽

Nuclear Localization Sequence ◽

Amyloid Aggregation ◽

Dynamic Phase ◽

Fibril Structure ◽

Cytoplasmic Transport ◽

Localization Sequence

AbstractHuman heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-β2 (Kapβ2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapβ2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminate structural understandings on the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapβ2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis.

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Insights into biological functions across species: examining the role of Rab proteins in YIP1 family function

Biochemical Society Transactions ◽

10.1042/bst0330614 ◽

2005 ◽

Vol 33 (4) ◽

pp. 614-618 ◽

Cited By ~ 6

Author(s):

C.Z. Chen ◽

R.N. Collins

Keyword(s):

Membrane Proteins ◽

Protein Function ◽

Evolutionary Conservation ◽

Biological Role ◽

Rab Proteins ◽

Biological Functions ◽

Human Homologue ◽

Family Function ◽

Evolutionarily Conserved

The YIP1 family comprises an evolutionarily conserved group of membrane proteins, which share the ability to bind di-prenylated Rab proteins. The biochemical capability of YIP1 family proteins suggests a possible role in the cycle of physical localization of Rab proteins between their cognate membranes and the cytosol. YIP1 is essential for viability in yeast and a deletion of YIP1 can be rescued with the human homologue YIP1A. We have made use of this evolutionary conservation of function to generate a series of mutant alleles of YIP1 to investigate the biological role of Yip1p. Our findings indicate evidence for the participation of Yip1p in both Rab and COPII protein function; at present, we are not able to distinguish between the models that these roles represent, i.e. independent or dependent activities of Yip1p.

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Comparative Genomics Reveals Long, Evolutionarily Conserved, Low-Complexity Islands in Yeast Proteins

Journal of Molecular Evolution ◽

10.1007/s00239-005-0291-0 ◽

2006 ◽

Vol 63 (3) ◽

pp. 415-425 ◽

Cited By ~ 7

Author(s):

Philip A. Romov ◽

Fubin Li ◽

Peter N. Lipke ◽

Susan L. Epstein ◽

Wei-Gang Qiu

Keyword(s):

Comparative Genomics ◽

Low Complexity ◽

Evolutionarily Conserved

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Bioinformatics Analysis of Evolution and Human Disease Related Transposable Element-Derived microRNAs

Life ◽

10.3390/life10060095 ◽

2020 ◽

Vol 10 (6) ◽

pp. 95

Author(s):

Hee-Eun Lee ◽

Jae-Won Huh ◽

Heui-Soo Kim

Keyword(s):

Transposable Element ◽

Human Disease ◽

Bioinformatics Analysis ◽

General Knowledge ◽

Theoretical Understanding ◽

Diverse Species ◽

Bioinformatics Tools ◽

Non Coding Rnas

Transposable element (TE) has the ability to insert into certain parts of the genome, and due to this event, it is possible for TEs to generate new factors and one of these factors are microRNAs (miRNA). miRNAs are non-coding RNAs made up of 19 to 24 nucleotides and numerous miRNAs are derived from TE. In this study, to support general knowledge on TE and miRNAs derived from TE, several bioinformatics tools and databases were used to analyze miRNAs derived from TE in two aspects: evolution and human disease. The distribution of TEs in diverse species presents that almost half of the genome is covered with TE in mammalians and less than a half in other vertebrates and invertebrates. Based on selected evolution-related miRNAs studies, a total of 51 miRNAs derived from TE were found and analyzed. For the human disease-related miRNAs, total of 34 miRNAs derived from TE were organized from the previous studies. In summary, abundant miRNAs derived from TE are found, however, the function of miRNAs derived from TE is not informed either. Therefore, this study provides theoretical understanding of miRNAs derived from TE by using various bioinformatics tools.

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Catechins as Tools to Understand the Molecular Basis of Neurodegeneration

Molecules ◽

10.3390/molecules25163571 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3571

Author(s):

Karla Martinez Pomier ◽

Rashik Ahmed ◽

Giuseppe Melacini

Keyword(s):

Phenolic Compounds ◽

Neurodegenerative Disorders ◽

Molecular Basis ◽

Protein Misfolding ◽

Molecular Mechanisms ◽

Amyloid Aggregation ◽

Amyloid Aggregates ◽

Parkinson’S Diseases ◽

Pharmacokinetic Properties ◽

Self Association

Protein misfolding as well as the subsequent self-association and deposition of amyloid aggregates is implicated in the progression of several neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Modulators of amyloidogenic aggregation serve as essential tools to dissect the underlying molecular mechanisms and may offer insight on potential therapeutic solutions. These modulators include green tea catechins, which are potent inhibitors of amyloid aggregation. Although catechins often exhibit poor pharmacokinetic properties and bioavailability, they are still essential tools for identifying the drivers of amyloid aggregation and for developing other aggregation modulators through structural mimicry. As an illustration of such strategies, here we review how catechins have been used to map the toxic surfaces of oligomeric amyloid-like species and develop catechin-based phenolic compounds with enhanced anti-amyloid activity.

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