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Global pentapeptide statistics are far away from expected distributions
Get PDFThe relationships between polypeptide composition, sequence, structure and function have been puzzling biologists ever since first protein sequences were determined. Here, we study the statistics of occurrence of all possible pentapeptide sequences in known proteins. To compensate for the non-uniform distribution of individual amino acid residues in protein sequences, we investigate separately all possible permutations of every given amino acid composition. For the majority of permutation groups we find that pentapeptide occurrences deviate strongly from the expected binomial distributions, and that the observed distributions are also characterized by high numbers of outlier sequences. An analysis of identified outliers shows they often contain known motifs and rare amino acids, suggesting that they represent important functional elements. We further compare the pentapeptide composition of regions known to correspond to protein domains with that of non-domain regions. We find that a substantial number of pentapeptides is clearly strongly favored in protein domains. Finally, we show that over-represented pentapeptides are significantly related to known functional motifs and to predicted ancient structural peptides
Insight into heavy metal resistome of soil psychrotolerant bacteria originating from King George Island (Antarctica)
Get PDFThe presence of heavy metals in Antarctica is an emerging issue, especially as (bio)weathering of metal-containing minerals occurs and human influence is more and more visible in this region. Chemical analysis of three soil samples collected from the remote regions of King George Island (Antarctica) revealed the presence of heavy metals (mainly copper, mercury, and zinc) at relatively high concentrations. Physiological characterization of over 200 heavy metal-resistant, psychrotolerant bacterial strains isolated from the Antarctic soil samples was performed. This enabled an insight into the heavy metal resistome of these cultivable bacteria and revealed the prevalence of co-resistance phenotypes. All bacteria identified in this study were screened for the presence of selected heavy metal-resistance genes, which resulted in identification of arsB (25), copA (3), czcA (33), and merA (26) genes in 62 strains. Comparative analysis of their nucleotide sequences provided an insight into the diversity of heavy metal-resistance genes in Antarctic bacteria
Interplay between Copper, Neprilysin, and N-Truncation of β-Amyloid
No full textSporadic Alzheimer's disease (AD) is associated with an inefficient clearance of the β-amyloid (Aβ) peptide from the central nervous system. The protein levels and activity of the Zn2+-dependent endopeptidase neprilysin (NEP) inversely correlate with brain Aβ levels during aging and in AD. The present study considered the ability of Cu2+ ions to inhibit human recombinant NEP and the role for NEP in generating N-truncated Aβ fragments with high-affinity Cu2+ binding motifs that can prevent this inhibition. Divalent copper noncompetitively inhibited NEP ( Ki = 1.0 μM), while proteolysis of Aβ yielded the soluble, Aβ4-9 fragment that can bind Cu2+ with femtomolar affinity at pH 7.4. This provides Aβ4-9 with the potential to act as a Cu2+ carrier and to mediate its own production by preventing NEP inhibition. Enzyme inhibition at high Zn2+ concentrations ( Ki = 20 μM) further suggests a mechanism for modulating NEP activity, Aβ4-9 production, and Cu2+ homeostasis
Diversity of Cell Wall Related Proteins in Human Pathogenic Fungi
Get PDFThe cell wall is one of the major keys to fungal identity. Fungi use their cell wall to sense the environment, and localize nutrients and competing microorganism. Pathogenic species additionally modify their cell walls to hide from a host’s immune system. With the growing number of fungal infections and alarming shortage of available drugs, we are in need of new approaches to fight pathogens. The cell wall seems to be a natural target, since animal host cells are devoid of it. The current knowledge about fungal cell wall components is often limited, and there is huge diversity both in structure and composition between species. In order to compare the distribution of diverse proteins involved in cell wall biosynthesis and maintenance, we performed sequence homology searches against 24 fungal proteomes from distinct taxonomic groups, all reported as human pathogens. This approach led to identification of 4014 cell wall proteins (CWPs), and enabled us to speculate about cell wall composition in recently sequenced pathogenic fungi with limited experimental information. We found large expansions of several CWP families, in particular taxa, and a number of new CWPs possibly involved in evading host immune recognition. Here, we present a comprehensive evolutionary history of fungal CWP families in the context of the fungal tree of life
Oxidation products of 5-methyl cytosine are decreased in senescent cells and tissues of progeroid mice
Get PDF5-Hydroxymethylcytosine and 5-formylcytosine are stable DNA base modifications generated from 5-methylcytosine by the ten-eleven translocation protein family that function as epigenetic markers. 5-Hydroxymethyluracil may also be generated from thymine by ten-eleven translocation enzymes. Here, we asked if these epigenetic changes accumulate in senescent cells, since they are thought to be inversely correlated with proliferation. Testing this in ERCC1-XPF-deficient cells and mice also enabled discovery if these DNA base changes are repaired by nucleotide excision repair. Epigenetic marks were measured in proliferating, quiescent and senescent wild-type (WT) and Ercc1−/− primary mouse embryonic fibroblasts. The pattern of epigenetic marks depended more on the proliferation status of the cells than their DNA repair capacity. The cytosine modifications were all decreased in senescent cells compared to quiescent or proliferating cells, whereas 5-(hydroxymethyl)-2′-deoxyuridine was increased. In vivo, both 5-(hydroxymethyl)-2′-deoxyuridine and 5-(hydroxymethyl)-2′-deoxycytidine were significantly increased in liver tissues of aged WT mice compared to young adult WT mice. Livers of Ercc1-deficient mice with premature senescence and aging had reduced level of 5-(hydroxymethyl)-
2′-deoxycytidine and 5-formyl-2′-deoxycytidine compared to aged-matched WT controls. Taken together, we demonstrate for the first time, that 5-(hydroxymethyl)-2′-deoxycytidine is significantly reduced in senescent cells and tissue, potentially yielding a novel marker of senescence
Plasmids of Psychrotolerant Polaromonas spp. Isolated From Arctic and Antarctic Glaciers – Diversity and Role in Adaptation to Polar Environments
Get PDFCold-active bacteria of the genus Polaromonas (class Betaproteobacteria) are important components of glacial microbiomes. In this study, extrachromosomal replicons of 26 psychrotolerant Polaromonas strains, isolated from Arctic and Antarctic glaciers, were identified, sequenced, and characterized. The plasmidome of these strains consists of 13 replicons, ranging in size from 3,378 to 101,077 bp. In silico sequence analyses identified the conserved backbones of these plasmids, composed of genes required for plasmid replication, stable maintenance, and conjugal transfer. Host range analysis revealed that all of the identified plasmids are narrow-host-range replicons, only able to replicate in bacteria of closely related genera (Polaromonas and Variovorax) of the Comamonadaceae family. Special attention was paid to the identification of plasmid auxiliary genetic information, which may contribute to the adaptation of bacteria to environmental conditions occurring in glaciers. Detailed analysis revealed the presence of genes encoding proteins potentially involved in (i) protection against reactive oxygen species, ultraviolet radiation, and low temperatures; (ii) transport and metabolism of organic compounds; (iii) transport of metal ions; and (iv) resistance to heavy metals. Some of the plasmids also carry genes required for the molecular assembly of iron–sulfur [Fe-S] clusters. Functional analysis of the predicted heavy metal resistance determinants demonstrated that their activity varies, depending on the host strain. This study provides the first molecular insight into the mobile DNA of Polaromonas spp. inhabiting polar glaciers. It has generated valuable data on the structure and properties of a pool of plasmids and highlighted their role in the biology of psychrotolerant Polaromonas strains and their adaptation to the environmental conditions of Arctic and Antarctic glaciers
Phylogenetic and Phylogenomic Definition of Rhizopus Species
Get PDFPhylogenomic approaches have the potential to improve confidence about the inter-relationships of species in the order Mucorales within the fungal tree of life. Rhizopus species are especially important as plant and animal pathogens and bioindustrial fermenters for food and metabolite production. A dataset of 192 orthologous genes was used to construct a phylogenetic tree of 21 Rhizopus strains, classified into four species isolated from habitats of industrial, medical and environmental importance. The phylogeny indicates that the genus Rhizopus consists of three major clades, with R. microsporus as the basal species and the sister lineage to R. stolonifer and two closely related species R. arrhizus and R. delemar A comparative analysis of the mating type locus across Rhizopus reveals that its structure is flexible even between different species in the same genus, but shows similarities between Rhizopus and other mucoralean fungi. The topology of single-gene phylogenies built for two genes involved in mating is similar to the phylogenomic tree. Comparison of the total length of the genome assemblies showed that genome size varies by as much as three-fold within a species and is driven by changes in transposable element copy numbers and genome duplications
The complete chloroplast genome of Colobanthus apetalus (Labill.) Druce: genome organization and comparison with related species
Get PDFColobanthus apetalus is a member of the genus Colobanthus, one of the 86 genera of
the large family Caryophyllaceae which groups annual and perennial herbs (rarely
shrubs) that are widely distributed around the globe, mainly in the Holarctic. The genus
Colobanthus consists of 25 species, including Colobanthus quitensis, an extremophile
plant native to the maritime Antarctic. Complete chloroplast (cp) genomes are useful
for phylogenetic studies and species identification. In this study, next-generation
sequencing (NGS) was used to identify the cp genome of C. apetalus. The complete
cp genome of C. apetalus has the length of 151,228 bp, 36.65% GC content, and a
quadripartite structure with a large single copy (LSC) of 83,380 bp and a small single
copy (SSC) of 17,206 bp separated by inverted repeats (IRs) of 25,321 bp. The cp genome
contains 131 genes, including 112 unique genes and 19 genes which are duplicated in
the IRs. The group of 112 unique genes features 73 protein-coding genes, 30 tRNA
genes, four rRNA genes and five conserved chloroplast open reading frames (ORFs).
A total of 12 forward repeats, 10 palindromic repeats, five reverse repeats and three
complementary repeats were detected. In addition, a simple sequence repeat (SSR)
analysis revealed 41 (mono-, di-, tri-, tetra-, penta- and hexanucleotide) SSRs, most of
which were AT-rich. A detailed comparison of C. apetalus and C. quitensis cp genomes
revealed identical gene content and order. A phylogenetic tree was built based on
the sequences of 76 protein-coding genes that are shared by the eleven sequenced
representatives of Caryophyllaceae and C. apetalus, and it revealed that C. apetalus and
C. quitensis form a clade that is closely related to Silene species and Agrostemma githago.
Moreover, the genus Silene appeared as a polymorphic taxon. The results of this study
expand our knowledge about the evolution and molecular biology of Caryophyllaceae
Β-defensins – Underestimated peptides in influenza combat
Get PDFDefensins are a family of host defense peptides present in vertebrates, invertebrates and plants. They display broad antimicrobial activity and immunomodulatory functions. Herein, the natural anti-influenzal role of β-defensins, as well as their potential usage as anti-influenza vaccine adjuvants and therapeutic agents, is reviewed. This article summarizes previously published information on β-defensin modes of action, expression changes after influenza infection and vaccination, biotechnological usage and possible boosting of their production by dietary supplementation
Orchestrated control of filaggrin-actin scaffolds underpins cornification.
Get PDFEpidermal stratification critically depends on keratinocyte differentiation and programmed death by cornification, leading to formation of a protective skin barrier. Cornification is dynamically controlled by the protein filaggrin, rapidly released from keratohyalin granules (KHGs). However, the mechanisms of cornification largely remain elusive, partly due to limitations of the observation techniques employed to study filaggrin organization in keratinocytes. Moreover, while the abundance of keratins within KHGs has been well described, it is not clear whether actin also contributes to their formation or fate. We employed advanced (super-resolution) microscopy to examine filaggrin organization and dynamics in skin and human keratinocytes during differentiation. We found that filaggrin organization depends on the cytoplasmic actin cytoskeleton, including the role for α- and β-actin scaffolds. Filaggrin-containing KHGs displayed high mobility and migrated toward the nucleus during differentiation. Pharmacological disruption targeting actin networks resulted in granule disintegration and accelerated cornification. We identified the role of AKT serine/threonine kinase 1 (AKT1), which controls binding preference and function of heat shock protein B1 (HspB1), facilitating the switch from actin stabilization to filaggrin processing. Our results suggest an extended model of cornification in which filaggrin utilizes actins to effectively control keratinocyte differentiation and death, promoting epidermal stratification and formation of a fully functional skin barrier