62 research outputs found

    Crystal structure of the YffB protein from Pseudomonas aeruginosa suggests a glutathione-dependent thiol reductase function

    Get PDF
    BACKGROUND: The yffB (PA3664) gene of Pseudomonas aeruginosa encodes an uncharacterized protein of 13 kDa molecular weight with a marginal sequence similarity to arsenate reductase from Escherichia coli. The crystal structure determination of YffB was undertaken as part of a structural genomics effort in order to assist with the functional assignment of the protein. RESULTS: The structure was determined at 1.0 Å resolution by single-wavelength anomalous diffraction. The fold is very similar to that of arsenate reductase, which is an extension of the thioredoxin fold. CONCLUSION: Given the conservation of the functionally important residues and the ability to bind glutathione, YffB is likely to function as a GSH-dependent thiol reductase

    SFPQ and Tau: critical factors contributing to rapid progression of Alzheimer's disease

    Get PDF
    Dysfunctional RNA-binding proteins (RBPs) have been implicated in several neurodegenerative disorders. Recently, this paradigm of RBPs has been extended to pathophysiology of Alzheimer's disease (AD). Here, we identified disease subtype specific variations in the RNA-binding proteome (RBPome) of sporadic AD (spAD), rapidly progressive AD (rpAD), and sporadic Creutzfeldt Jakob disease (sCJD), as well as control cases using RNA pull-down assay in combination with proteomics. We show that one of these identified proteins, splicing factor proline and glutamine rich (SFPQ), is downregulated in the post-mortem brains of rapidly progressive AD patients, sCJD patients and 3xTg mice brain at terminal stage of the disease. In contrast, the expression of SFPQ was elevated at early stage of the disease in the 3xTg mice, and in vitro after oxidative stress stimuli. Strikingly, in rpAD patients' brains SFPQ showed a significant dislocation from the nucleus and cytoplasmic colocalization with TIA-1. Furthermore, in rpAD brain lesions, SFPQ and p-tau showed extranuclear colocalization. Of note, association between SFPQ and tau-oligomers in rpAD brains suggests a possible role of SFPQ in oligomerization and subsequent misfolding of tau protein. In line with the findings from the human brain, our in vitro study showed that SFPQ is recruited into TIA-1-positive stress granules (SGs) after oxidative stress induction, and colocalizes with tau/p-tau in these granules, providing a possible mechanism of SFPQ dislocation through pathological SGs. Furthermore, the expression of human tau in vitro induced significant downregulation of SFPQ, suggesting a causal role of tau in the downregulation of SFPQ. The findings from the current study indicate that the dysregulation and dislocation of SFPQ, the subsequent DNA-related anomalies and aberrant dynamics of SGs in association with pathological tau represents a critical pathway which contributes to rapid progression of AD

    The Russian database of HIV antiretroviral drug resistance

    Get PDF
    The development of sequencing technologies and bioinformatic analysis made it possible to conduct molecular and epidemiological studies, in which nucleotide sequences of the human immunodeficiency virus (HIV) are used as information added to the patient profile. From a practical perspective, studies of prevalence of HIV drug resistance (HIVDR) are of the highest significance. To promote such studies, different countries use databases that serve as repositories of genetic and epidemiological information. The Russian HIVDR database (https://hivresist.ru/) was created in 2009. Nevertheless, it was characterized by limited applicability for a long time. Since 2021, after the regulatory documents had been revised and updated, the entry of HIVDR research results into the Russian HIVDR database has been mandatory. Therefore, the priority attention has been given to upgrading the database and improving its functional capabilities. Different methods have been developed to enter clinical, epidemiological and genetic data. At the time of this study, the Russian database HIVDR contained 10,626 unique records about patients and 13,126 nucleotide sequences deposited by 10 institutions. The following functions have been provided for data analysis: quality control of the epidemiological and clinical information about a patient, quality control of nucleotide sequences, contamination check, subtyping, detection of DR mutations, identification of viral tropism and generation of standardized reports. The efforts toward further development of the Russian HIVDR database will be focused on designing tools for detection and analysis of molecular clusters, adaptation to routine application for epidemiological surveillance of HIV infection

    Hypothesis: AA amyloidosis is a factor causing systemic complications after coronavirus disease

    No full text
    The severe course of COVID-19 causes systemic chronic inflammation and thrombosis in a wide variety of organs and tissues. The nature of these inflammations remains a mystery, although they are known to occur against the background of a high level of cytokine production. The high level of cytokines provokes overproduction of the Serum amyloid A (SAA) protein. Moreover, the number of studies has shown that the severe COVID-19 causes SAA overproduction. The authors of these works regard a high level of SAA exclusively as a biomarker of COVID-19. However, it should be borne in mind that overproduction of SAA can cause systemic AA amyloidosis. SAA forms cytotoxic amyloid deposits in various organs and induces inflammation and thrombosis. The consequences of COVID-19 infection are surprisingly similar to the clinical picture that is observed in AA amyloidosis. Here I present the hypothesis that AA amyloidosis is a factor causing systemic complications after coronavirus disease

    Stress response is the main trigger of sporadic amyloidoses

    No full text
    Amyloidoses are a group of diseases associated with the formation of pathological protein fibrils with cross-β structures. Approximately 5–10% of the cases of these diseases are determined by amyloidogenic mutations, as well as by transmission of infectious amyloids (prions) between organisms. The most common group of so-called sporadic amyloidoses is associated with abnormal aggregation of wild-type proteins. Some sporadic amyloidoses are known to be induced only against the background of certain pathologies, but in some cases the cause of amyloidosis is unclear. It is assumed that these diseases often occur by accident. Here we present facts and hypotheses about the association of sporadic amyloidoses with vascular pathologies, trauma, oxidative stress, cancer, metabolic diseases, chronic infections and COVID-19. Generalization of current data shows that all sporadic amyloidoses can be regarded as a secondary event occurring against the background of diseases provoking a cellular stress response. Various factors causing the stress response provoke protein overproduction, a local increase in the concentration or modifications, which contributes to amyloidogenesis. Progress in the treatment of vascular, metabolic and infectious diseases, as well as cancers, should lead to a significant reduction in the risk of sporadic amyloidoses

    THE INVESTIGATION OF THE MOBILE HOBO-ELEMENTS IN THE GENOME OF THE AFFINED LINES DROSOPHILA MELANOGASTER, TO BE CONTINUOUSLY SELECTED

    No full text
    It has been established, that the mobile hobo-elements are the sources of the genetic heterogenicity in the genome of the low-active inbred line NA. A selection by the adaptively important signs brings to the active transposition of the hobo-elements, the variation of the full-dimensional and deleted fraction hobo and directed variation of the disgenic characteristics. With the isogenisation of the chromosomes of the NA line, a high site-specificity of the transposition has been notedAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

    Amyloid Properties of the FXR1 Protein Are Conserved in Evolution of Vertebrates

    No full text
    Functional amyloids are fibrillary proteins with a cross-β structure that play a structural or regulatory role in pro- and eukaryotes. Previously, we have demonstrated that the RNA-binding FXR1 protein functions in an amyloid form in the rat brain. This RNA-binding protein plays an important role in the regulation of long-term memory, emotions, and cancer. Here, we evaluate the amyloid properties of FXR1 in organisms representing various classes of vertebrates. We show the colocalization of FXR1 with amyloid-specific dyes in the neurons of amphibians, reptiles, and birds. Moreover, FXR1, as with other amyloids, forms detergent-resistant insoluble aggregates in all studied animals. The FXR1 protein isolated by immunoprecipitation from the brains of different vertebrate species forms fibrils, which show yellow-green birefringence after staining with Congo red. Our data indicate that in the evolution of vertebrates, FXR1 acquired amyloid properties at least 365 million years ago. Based on the obtained data, we discuss the possible role of FXR1 amyloid fibrils in the regulation of vital processes in the brain of vertebrates
    corecore