Biology subjects

Ziganshin, R.

Publications and source records attributed to Ziganshin, R..

7 recordsLinked to original sources

bioRxiv2026

A Method to Analyze Low-Quality Archaic Human Genomes and its Application to the Teshik-Tash 1 Neandertal

The Teshik-Tash 1 child whose remains were found in Uzbekistan represents the southeastern-most extent of the known Neandertal range, providing an important link with the better studied Caucasus and Altai Mountain ranges. However, due to poor DNA preservation, studying the genetics of Teshik Tash 1 has remained elusive. Here we present analyses of the nuclear DNA from the Teshik-Tash 1, from extracts that are highly contaminated with present-day human DNA. To achieve this, we developed a new computational method, admixslug, that jointly models contamination and population relationships, in order to infer the relationship of a target individual from which only low-quality nuclear DNA is available, to high-quality archaic human genomes. After validating admixslug, we show that Teshik-Tash 1 is genetically more similar to later Neandertals from Western Eurasia than to older Neandertals from the Altai Mountains. We estimate that Teshik-Tash 1 split from the Western Eurasian lineage between 80,000 and 100,000 years ago. Despite the geographical proximity of Teshik-Tash 1 to the Denisovan range, we find no evidence for Denisovan ancestry in his genome. Our results demonstrate that admixslug enables the study of archaic human specimens in cases where DNA preservation was previously considered too poor for population genetic analyses.

genetics↗

bioRxiv2022

Vexitoxins: a novel class of conotoxin-like venom peptides from predatory gastropods of the genus Vexillum

Venoms of predatory marine cone snails (the family Conidae, order Neogastropoda) are intensely studied because of the broad range of biomedical applications of the neuropeptides that they contain, conotoxins. Meanwhile anatomy in some other neogastropod lineages strongly suggests that they have evolved similar venoms independently of cone snails, nevertheless their venom composition remains unstudied. Here we focus on the most diversified of these lineages, the genus Vexillum (the family Costellariidae). We have generated comprehensive multi-specimen, multi-tissue RNA-Seq data sets for three Vexillum species, and supported our findings in two species by proteomic profiling. We show that venoms of Vexillum are dominated by highly diversified short cysteine-rich peptides that in many aspects are very similar to conotoxins. Vexitoxins possess the same precursor organization, display overlapping cysteine frameworks and share several common post-translational modifications with conotoxins. Some vexitoxins show detectable sequence similarity to conotoxins, and are predicted to adopt similar domain conformations, including a pharmacologically relevant inhibitory cysteine-know motif (ICK). The tubular gL of Vexillum is a notably more recent evolutionary novelty than the conoidean venom gland. Thus, we hypothesize lower divergence between the toxin genes, and their somatic counterparts compared to that in conotoxins, and we find support for this hypothesis in the molecular evolution of the vexitoxin cluster V027. We use this example to discuss how future studies on vexitoxins can inform origin and evolution of conotoxins, and how they may help addressing standing questions in venom evolution.

biochemistry↗

bioRxiv2022

Validating amino acid variants in proteogenomics using sequence coverage by multiple reads

Mass spectrometry-based proteome analysis usually implies matching mass spectra of proteolytic peptides to amino acid sequences predicted from nucleic acid sequences. At the same time, due to the stochastic nature of the method when it comes to proteome-wide analysis, in which only a fraction of peptides are selected for sequencing, the completeness of protein sequence identification is undermined. Likewise, the reliability of peptide variant identification in proteogenomic studies is suffering. We propose a way to interpret shotgun proteomics results, specifically in data-dependent acquisition mode, as protein sequence coverage by multiple reads, just as it is done in the field of nucleic acid sequencing for the calling of single nucleotide variants. Multiple reads for each position in a sequence could be provided by overlapping distinct peptides, thus, confirming the presence of certain amino acid residues in the overlapping stretch with much lower false discovery rate than conventional 1%. The source of overlapping distinct peptides are, first, miscleaved tryptic peptides in combination with their properly cleaved counterparts, and, second, peptides generated by several proteases with different specificities after the same specimen is subject to parallel digestion and analyzed separately. We illustrate this approach using publicly available multiprotease proteomic datasets and our own data generated for HEK-293 cell line digests obtained using trypsin, LysC and GluC proteases. From 5000 to 8000 protein groups are identified for each digest corresponding to up to 30% of the whole proteome coverage. Most of this coverage was provided by a single read, while up to 7% of the observed protein sequences were covered two-fold and more. The proteogenomic analysis of HEK-293 cell line revealed 36 peptide variants associated with SNP, seven of which were supported by multiple reads. The efficiency of the multiple reads approach depends strongly on the depth of proteome analysis, the digesting features such as the level of miscleavages, and will increase with the number of different proteases used in parallel proteome digestion. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/475497v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@1d6ee2org.highwire.dtl.DTLVardef@5ae8baorg.highwire.dtl.DTLVardef@652216org.highwire.dtl.DTLVardef@1a0d49b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2021

FAMOSS, a conserved 41-aa peptide involved in plant tip growth regulation

Recent evidence shows that small open reading frame (smORF; <100 codons)-encoded peptides (SEPs) containing transmembrane domains are preadapted to be progenitors of novel functional genes. A dozen of such SEPs translated from long non-coding RNAs (lncRNAs) are already functionally characterised in animals. However, functional plant lncRNA-smORF-coded peptides are not yet described. Here, we report detailed functional characterization of a 41-aa peptide encoded by lncRNA-smORFs in the moss Physcomitrium patens, which was named "FAst-growing MOSS" (FAMOSS). We found that the FAMOSS interacts with the Rab-type small GTPase proteins and its overexpression leads to faster moss growth rate and more intensive vesicular transport in apical cells, while its knockout results in the opposite effect. The FAMOSS contains a predicted transmembrane domain and possible orthologs from streptophyta algae to flowering plants have a very conserved structure. Thus, the FAMOSS peptide is a previously unknown conserved player of Rab-mediated processes in plants. Our findings are in line with functional studies of transmembrane SEPs in animals and prove the principles of SEPs evolution. This study provides new insights into functions of plant lncRNA-smORFs.

plant biology↗

bioRxiv2020

LC-MS/MS analysis of lesional and normally looking psoriatic skin reveals significant changes in protein metabolism and RNA processing

BackgroundPlaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available. AimThe aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease. MethodsSkin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients skin compared to skin of the healthy volunteers. ResultsThe performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. We discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG in normally looking skin of the patients. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes. ConclusionOur findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease. Data are available via ProteomeXchange with identifier PXD021673.

genetics↗

bioRxiv2019

Crystal Structure of the putative tail fiber protein gp53 from the Acinetobacter baumannii bacteriophage AP22

This report describes the structure of a putative tail fiber protein of the Acinetobacter baumannii bacteriophage AP22. The target host range of strictly lytic bacteriophage AP22 includes many clinical isolates of A. baumannii from hospitals in Chelyabinsk, Nizhny Novgorod, Moscow and St. Petersburg (Russia), but its host cell binding apparatus remains uncharacterized. Here, we report the crystal structure of the C-terminal fragment of AP22 gene product 53 (gp53) one of its two putative host cell-binding proteins. We show that gp53 forms a trimeric fiber and binds ethylene glycol and glycerol molecules that represent known surrogates of the oligosaccharide backbone. However, despite its structural similarities to other phage/virus host cell-binding fibers and its binding to small sugar-like molecules, gp53 did not inhibit AP22 infection and its role in the infection process remains unclear.

biophysics↗

bioRxiv2018

Luciferase of the Japanese syllid polychaete Odontosyllis umdecimdonta

1Odontosyllis undecimdonta is a marine syllid polychaete that produces bright internal and exuded bioluminescence. Despite over fifty years of biochemical investigation into Odontosyllis bioluminescence, the light-emitting small molecule substrate and catalyzing luciferase protein have remained a mystery. Here we describe the discovery of a bioluminescent protein fraction from O. undecimdonta, the identification of the luciferase using peptide and RNA sequencing, and the in vitro reconstruction of the bioluminescence reaction using highly purified O. undecimdonta luciferin and recombinant luciferase. Lastly, we found no identifiably homologous proteins in publicly available datasets. This suggests that the syllid polychaetes contain an evolutionarily unique luciferase among all characterized luminous taxa.\n\n3 HighlightsO_LIThe polychaete O. undecimdonta uses a luciferin-luciferase bioluminescence system\nC_LIO_LIO. undecimdonta bioluminescence does not require additional cofactors\nC_LIO_LIThe luciferase of the Japanese fireworm is 329 amino acids long\nC_LIO_LIRecombinant luciferase is not secreted when expressed in human cells\nC_LIO_LIExogenous luciferin does not seem to penetrate cell membranes-only lysate luminesces\nC_LIO_LIThe luciferase transcript is supported by full-length cDNA reads with 5 and 3 UTR\nC_LI\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC=\"FIGDIR/small/329631_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (25K):\norg.highwire.dtl.DTLVardef@15882beorg.highwire.dtl.DTLVardef@1efc214org.highwire.dtl.DTLVardef@1aee561org.highwire.dtl.DTLVardef@15582b7_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗