Role of the Gut Microbiome and Bacterial Amyloids in the Development of Synucleinopathies.

Less than ten years ago, evidence began to accumulate about association between the changes in the composition of gut microbiota and development of human synucleinopathies, in particular sporadic form of Parkinson's disease. We collected data from more than one hundred and thirty experimental studies that reported similar results and summarized the frequencies of detection of different groups of bacteria in these studies. It is important to note that it is extremely rare that a unidirectional change in the population of one or another group of microorganisms (only an elevation or only a reduction) was detected in the patients with Parkinson's disease.

How Big Is the Yeast Prion Universe?

The number of yeast prions and prion-like proteins described since 1994 has grown from two to nearly twenty. If in the early years most scientists working with the classic mammalian prion, PrP, were skeptical about the possibility of using the term prion to refer to yeast cytoplasmic elements with unusual properties, it is now clear that prion-like phenomena are widespread and that yeast can serve as a convenient model for studying them. Here we give a brief overview of the yeast prions discovered so far and focus our attention to the various approaches used to identify them.

Identification of New FG-Repeat Nucleoporins with Amyloid Properties.

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.

The [PSI] prion modulates cytochrome oxidase deficiency caused by deletion of .

Cytochrome oxidase (CcO) is a pivotal enzyme of the mitochondrial respiratory chain, which sustains bioenergetics of eukaryotic cells. Cox12, a peripheral subunit of CcO oxidase, is required for full activity of the enzyme, but its exact function is unknown. Here experimental evolution of a Δ strain for ∼300 generations allowed to restore the activity of CcO oxidase.

NOS1AP Interacts with α-Synuclein and Aggregates in Yeast and Mammalian Cells.

The gene encodes a cytosolic protein that binds to the signaling cascade component neuronal nitric oxide synthase (nNOS). It is associated with many different disorders, such as schizophrenia, post-traumatic stress disorder, autism, cardiovascular disorders, and breast cancer. The NOS1AP (also known as CAPON) protein mediates signaling within a complex which includes the NMDA receptor, PSD-95, and nNOS.

Amyloid fibril length distribution from dynamic light scattering data.

The study of the aggregation of amyloid proteins is challenging. A new approach to processing dynamic light scattering data was developed and tested using aggregates of the well-known model Sup35NM amyloid. After filtering and calculating the moving averages of autocorrelation functions to reduce impacts of noise, each averaged autocorrelation function is converted to the fibril length distribution via numerical modeling.

The Human NUP58 Nucleoporin Can Form Amyloids In Vitro and In Vivo.

Amyloids are fibrillar protein aggregates with a cross-β structure and unusual features, including high resistance to detergent or protease treatment. More than two hundred different proteins with amyloid or amyloid-like properties are already known. Several examples of nucleoporins (e.

Symmetry Breaking in an Excited Quadrupolar Acridine-Dione Derivative Driven by Hydrogen Bonding.

An acridine-dione derivative (3,3,11,11-tetramethyl-8,16-diphenyl-3,4,8,10,11,12,13,16-octahydroacridino[4,3-]acridine-1.9(2,5)dion) with quadrupolar motif has been synthesized and its stationary and transient spectra have been measured. Stationary absorption and fluorescence spectra as well as nonstationary spectra show no signs of symmetry breaking (SB) in aprotic solvents, even of high polarity.

The Role of Rotational Motion in Diffusion NMR Experiments on Supramolecular Assemblies: Application to Sup35NM Fibrils.

Pulsed-field gradient (PFG) NMR is an important tool for characterization of biomolecules and supramolecular assemblies. However, for micrometer-sized objects, such as amyloid fibrils, these experiments become difficult to interpret because in addition to translational diffusion they are also sensitive to rotational diffusion. We have constructed a mathematical theory describing the outcome of PFG NMR experiments on rod-like fibrils.

Quantitative assessment of chaperone binding to amyloid aggregates identifies specificity of Hsp40 interaction with yeast prion fibrils.

Yeast self-perpetuating protein aggregates (yeast prions) provide a framework to investigate the interaction of misfolded proteins with the protein quality control machinery. The major component of this system that facilitates propagation of all known yeast amyloid prions is the Hsp104 chaperone that catalyzes fibril fragmentation. Overproduction of Hsp104 cures some yeast prions via a fragmentation-independent mechanism.

Estimation of amyloid aggregate sizes with semi-denaturing detergent agarose gel electrophoresis and its limitations.

Semi-denaturing detergent agarose gel electrophoresis (SDD-AGE) was proposed by Vitaly V. Kushnirov in the Michael D. Ter-Avanesyan's laboratory as a method to compare sizes of amyloid aggregates.

Nonsense Mutations in the Yeast Gene Affect the [] Prion Propagation.

The essential gene encodes yeast translation termination factor eRF3. Previously, we isolated nonsense mutations and proposed that the viability of such mutants can be explained by readthrough of the premature stop codon. Such mutations, as well as the prion [], can appear in natural yeast populations, and their combinations may have different effects on the cells.

Design of a New [ ]-No-More Mutation in With Strong Inhibitory Effect on the [ ] Prion Propagation.

A number of [ ]-no-more (PNM) mutations, eliminating [ ] prion, were previously described in . In this study, we designed and analyzed a new PNM mutation based on the parallel in-register β-structure of Sup35 prion fibrils suggested by the known experimental data. In such an arrangement, substitution of non-charged residues by charged ones may destabilize the fibril structure.

Spectral Dynamics of Nitro Derivatives of Xanthione in Solutions.

Nitro derivatives of xanthione, 2,7-dinitro-9 H-xanthene-9-thione and 2,4,7-trinitro-9 H-xanthene-9-thione, have been first synthesized and their stationary and transient spectra have been measured. The stationary spectra show that the attachment of the nitro groups to the xanthione scaffold leads to strong quenching of S → S fluorescence and the decrease of the oscillator strength of the S ← S electronic transition. Analysis of the transient absorption spectra uncovers the ultrafast stimulated emission quenching from the second excited state, S, in the both derivatives.

Low-Temperature Effect on the Electronic Structure and Spectral-Fluorescent Properties of Highly Dipolar Merocyanines.

Absorption and fluorescence spectra of a vinylogous series of reversely solvatochromic merocyanines based on benzimidazole and malononitrile have been studied in frozen ethanol solutions at 77 K. It is found that they possess negative thermochromism-in contrast to both positively solvatochromic merocyanines and negatively solvatochromic symmetrical ionic polymethines-and even stronger negative thermofluorochromism. It has been deduced from the spectral data that at low temperature their electronic structure becomes more dipolar, deviating substantially from the virtual ideal polymethine in both the ground and the excited states.

Protein Co-Aggregation Related to Amyloids: Methods of Investigation, Diversity, and Classification.

Amyloids are unbranched protein fibrils with a characteristic spatial structure. Although the amyloids were first described as protein deposits that are associated with the diseases, today it is becoming clear that these protein fibrils play multiple biological roles that are essential for different organisms, from archaea and bacteria to humans. The appearance of amyloid, first of all, causes changes in the intracellular quantity of the corresponding soluble protein(s), and at the same time the aggregate can include other proteins due to different molecular mechanisms.

Overproduction of Sch9 leads to its aggregation and cell elongation in Saccharomyces cerevisiae.

The Sch9 kinase of Saccharomyces cerevisiae is one of the major TOR pathway effectors and regulates diverse processes in the cell. Sch9 belongs to the AGC kinase family. In human, amplification of AGC kinase genes is connected with cancer.

BetaSerpentine: a bioinformatics tool for reconstruction of amyloid structures.

Motivation: Numerous experimental studies have suggested that polypeptide chains of large amyloidogenic regions zig-zag in β-serpentine arrangements. These β-serpentines are stacked axially and form the superpleated β-structure. Despite this progress in the understanding of amyloid folds, the determination of their 3D structure at the atomic level is still a problem due to the polymorphism of these fibrils and incompleteness of experimental structural data.

M60-like metalloprotease domain of the Escherichia coli YghJ protein forms amyloid fibrils.

Amyloids are protein fibrils with a characteristic spatial structure. Amyloids were long perceived as the pathogens involved in a set of lethal diseases in humans and animals. In recent decades, it has become clear that amyloids represent a quaternary protein structure that is not only pathological but also functionally important and is widely used by different organisms, ranging from archaea to animals, to implement diverse biological functions.

UV-Vis absorption spectra and electronic structure of merocyanines in the gas phase.

Gas-phase absorption spectra of a merocyanine vinylogous series have been studied for the first time. In vapour, their long-wavelength absorption bands were found to be considerably shifted hypsochromically, broader, more symmetrical, less intense, and their vinylene shift much smaller than even in low-polarity n-hexane. This indicates that in the gas phase their electronic structure closely approaches the nonpolar polyene limiting structure.

Allelic variants of hereditary prions: The bimodularity principle.

Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either "canonical" (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as "gene" and "allele" to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite.