scholarly journals Identification and characterization of histones in Physarum polycephalum evidence a phylogenetic vicinity of Mycetozoans to the animal kingdom

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Axel Poulet ◽  
Laxmi Narayan Mishra ◽  
Stéphane Téletchéa ◽  
Jeffrey J Hayes ◽  
Yannick Jacob ◽  
...  

Abstract Physarum polycephalum belongs to Mycetozoans, a phylogenetic clade apart from the animal, plant and fungus kingdoms. Histones are nuclear proteins involved in genome organization and regulation and are among the most evolutionary conserved proteins within eukaryotes. Therefore, this raises the question of their conservation in Physarum and the position of this organism within the eukaryotic phylogenic tree based on histone sequences. We carried out a comprehensive study of histones in Physarum polycephalum using genomic, transcriptomic and molecular data. Our results allowed to identify the different isoforms of the core histones H2A, H2B, H3 and H4 which exhibit strong conservation of amino acid residues previously identified as subject to post-translational modifications. Furthermore, we also identified the linker histone H1, the most divergent histone, and characterized a large number of its PTMs by mass spectrometry. We also performed an in-depth investigation of histone genes and transcript structures. Histone proteins are highly conserved in Physarum and their characterization will contribute to a better understanding of the polyphyletic Mycetozoan group. Our data reinforce that P. polycephalum is evolutionary closer to animals than plants and located at the crown of the eukaryotic tree. Our study provides new insights in the evolutionary history of Physarum and eukaryote lineages.

Author(s):  
Dmitrii S. Bug ◽  
Ildar M. Barkhatov ◽  
Yana V. Gudozhnikova ◽  
Artem V. Tishkov ◽  
Natalia V. Petukhova ◽  
...  

Osteopetrosis is a group of rare inheritable disorders of the skeleton characterized by increased bone density. The disease is remarkably heterogeneous in clinical presentation and often misdiagnosed. Therefore, genetic testing and molecular pathogenicity analysis are essential for precise diagnosis and new targets for preventive pharmacotherapy. Mutations in the CLCN7 gene give rise to the complete spectrum of osteopetrosis phenotypes and are responsible for about 75% of cases of autosomal dominant osteopetrosis. In this study, we report the identification of a novel variant in the CLCN7 gene in a patient diagnosed with osteopetrosis and provide evidence for its significance (likely deleterious) based on extensive comparative genomics, protein sequence and structure analysis. A set of automated bioinformatics tools used to predict consequences of this variant identified it as deleterious or pathogenic. Structure analysis revealed that the variant is located at the same “hot spot” as the most common CLCN7 mutations causing osteopetrosis. Deep phylogenetic reconstruction showed that not only Leu614Arg, but any non-aliphatic substitutions in this position are evolutionarily intolerant, further supporting the deleterious nature of the variant. The present study provides further evidence that reconstructing a precise evolutionary history of a gene helps predicting phenotypical consequences of variants of uncertain significance.


PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112762 ◽  
Author(s):  
Nathan Dissinger ◽  
Nikoloz Shkriabai ◽  
Sonja Hess ◽  
Jacob Al-Saleem ◽  
Mamuka Kvaratskhelia ◽  
...  

2013 ◽  
Vol 94 (3) ◽  
pp. 570-582 ◽  
Author(s):  
Chao-Ting Xiao ◽  
Luis G. Giménez-Lirola ◽  
Priscilla F. Gerber ◽  
Yong-Hou Jiang ◽  
Patrick G. Halbur ◽  
...  

Many astrovirus (AstV) species are associated with enteric disease, although extraintestinal manifestations in mammalian and avian hosts have also been described. In this study, the prevalence rates of porcine AstV types 1–5 (PAstV1–PAstV5) were investigated using faecal samples from 509 pigs of which 488 (95.9 %) came from farms with a history of diarrhoea. All of the five known PAstV types were found to circulate in pigs in the USA, and co-infection of a single pig with two or more PAstV types was frequently observed. A high overall prevalence of 64.0 % (326/509) of PAstV RNA-positive samples was detected, with 97.2 % (317/326) of the PAstV RNA-positive pigs infected with PAstV4. Further genomic sequencing and characterization of the selected isolates revealed low sequence identities (49.2–89.0 %) with known PAstV strains, indicating novel types or genotypes of PAstV2, PAstV4 and PAstV5. Some new features of the genomes of the PAstVs were also discovered. The first complete genome of a PAstV3 isolate was obtained and showed identities of 50.5–55.3 % with mink AstV and the novel human AstVs compared with 38.4–42.7 % with other PAstV types. Phylogenetic analysis revealed that PAstV1, PAstV2 and PAstV3 were more closely related to AstVs from humans and other animals than to each other, indicating past cross-species transmission and the zoonotic potential of these PAstVs.


2011 ◽  
Vol 17 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Alexander-Thomas Hauser ◽  
Elisabeth-Maria Bissinger ◽  
Eric Metzger ◽  
Antje Repenning ◽  
Uta-Maria Bauer ◽  
...  

In the past years, a lot of attention has been given to the identification and characterization of selective and potent inhibitors of chromatin-modifying enzymes to better understand their specific role in transcriptional regulation. As aberrant histone methylation is involved in different pathological processes, the search for methyltransferase and demethylase inhibitors has emerged as a crucial issue in current medicinal chemistry research. High-throughput in vitro assays are important tools for the identification of new methyltransferase or demethylase inhibitors. These usually use oligopeptide substrates derived from histone sequences, although in many cases, they are not good substrates for these enzymes. Here, the authors report about the setup and establishment of in vitro assays that use native core histones as substrates, enabling an assay environment that better resembles native conditions. They have applied these substrates for the known formaldehyde dehydrogenase assay for the histone demethylase LSD1 and have established two new antibody-based assays. For LSD1, a heterogeneous assay format was set up, and a homogeneous assay was used for the characterization of the arginine methyltransferase PRMT1. Validation of the system was achieved with reference inhibitors in each case.


2015 ◽  
Vol 10 (S314) ◽  
pp. 179-182
Author(s):  
Tara H. Cotten ◽  
Inseok Song

AbstractDebris disks are intimately linked to planetary system evolution since the rocky material surrounding the host stars is believed to be due to secondary generation from the collisions of planetesimals. With the conclusion and lack of future large scale infrared excess survey missions, it is time to summarize the history of using excess emission in the infrared as a tracer of debris and exploit all available data as well as provide a comprehensive study of the parameters of these important objects. We have compiled a catalog of infrared excess stars from peer-reviewed articles and performed an extensive search for new debris disks by cross-correlating the Tycho-2 and AllWISE catalogs. This study will conclude following the thorough examination of each debris disk star's parameters obtained through high-resolution spectroscopy at various facilities which is currently ongoing. We will maintain a webpage (www.debrisdisks.org) devoted to these infrared excess sources and provide various resources related to our catalog creation, SED fitting, and data reduction.


Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3144
Author(s):  
Dmitry Tikhonov ◽  
Liudmila Kulikova ◽  
Arthur Kopylov ◽  
Kristina Malsagova ◽  
Alexander Stepanov ◽  
...  

New advances in protein post-translational modifications (PTMs) have revealed a complex layer of regulatory mechanisms through which PTMs control cell signaling and metabolic pathways, contributing to the diverse metabolic phenotypes found in cancer. Using conformational templates and the three-dimensional (3D) environment investigation of proteins in patients with colorectal cancer, it was demonstrated that most PTMs (phosphorylation, acetylation, and ubiquitination) are localized in the supersecondary structures (helical pairs). We showed that such helical pairs are represented on the outer surface of protein molecules and characterized by a largely accessible area for the surrounding solvent. Most promising and meaningful modifications were observed on the surface of vitamin D-binding protein (VDBP), complement C4-A (CO4A), X-ray repair cross-complementing protein 6 (XRCC6), Plasma protease C1 inhibitor (IC1), and albumin (ALBU), which are related to colorectal cancer developing. Based on the presented data, we propose the impact of the observed modifications in immune response, inflammatory reaction, regulation of cell migration, and promotion of tumor growth. Here, we suggest a computational approach in which high-throughput analysis for identification and characterization of PTM signature, associated with cancer metabolic reprograming, can be improved to prognostic value and bring a new strategy to the targeted therapy.


2013 ◽  
Vol 79 (19) ◽  
pp. 5788-5798 ◽  
Author(s):  
Chang-Hao Cui ◽  
Qing-Mei Liu ◽  
Jin-Kwang Kim ◽  
Bong-Hyun Sung ◽  
Song-Gun Kim ◽  
...  

ABSTRACTHere, we isolated and characterized a new ginsenoside-transforming β-glucosidase (BglQM) fromMucilaginibactersp. strain QM49 that shows biotransformation activity for various major ginsenosides. The gene responsible for this activity,bglQM, consists of 2,346 bp and is predicted to encode 781 amino acid residues. This enzyme has a molecular mass of 85.6 kDa. Sequence analysis of BglQM revealed that it could be classified into glycoside hydrolase family 3. The enzyme was overexpressed inEscherichia coliBL21(DE3) using a maltose binding protein (MBP)-fused pMAL-c2x vector system containing the tobacco etch virus (TEV) proteolytic cleavage site. Overexpressed recombinant BglQM could efficiently transform the protopanaxatriol-type ginsenosides Re and Rg1into (S)-Rg2and (S)-Rh1, respectively, by hydrolyzing one glucose moiety attached to the C-20 position at pH 8.0 and 30°C. TheKmvalues forp-nitrophenyl-β-d-glucopyranoside, Re, and Rg1were 37.0 ± 0.4 μM and 3.22 ± 0.15 and 1.48 ± 0.09 mM, respectively, and theVmaxvalues were 33.4 ± 0.6 μmol min−1mg−1of protein and 19.2 ± 0.2 and 28.8 ± 0.27 nmol min−1mg−1of protein, respectively. A crude protopanaxatriol-type ginsenoside mixture (PPTGM) was treated with BglQM, followed by silica column purification, to produce (S)-Rh1and (S)-Rg2at chromatographic purities of 98% ± 0.5% and 97% ± 1.2%, respectively. This is the first report of gram-scale production of (S)-Rh1and (S)-Rg2from PPTGM using a novel ginsenoside-transforming β-glucosidase of glycoside hydrolase family 3.


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