Alexandra P. Yan, Paul A. Salnikov, Maria M. Gridina, Polina S. Belokopytova, Veniamin S. Fishman
{"title":"Towards Development of the 4C-Based Method Detecting Interactions of Plasmid DNA with Host Genome","authors":"Alexandra P. Yan, Paul A. Salnikov, Maria M. Gridina, Polina S. Belokopytova, Veniamin S. Fishman","doi":"10.1134/S0006297924040059","DOIUrl":"10.1134/S0006297924040059","url":null,"abstract":"<p>Chromosome conformation capture techniques have revolutionized our understanding of chromatin architecture and dynamics at the genome-wide scale. In recent years, these methods have been applied to a diverse array of species, revealing fundamental principles of chromosomal organization. However, structural organization of the extrachromosomal entities, like viral genomes or plasmids, and their interactions with the host genome, remain relatively underexplored. In this work, we introduce an enhanced 4C-protocol tailored for probing plasmid DNA interactions. We design specific plasmid vector and optimize protocol to allow high detection rate of contacts between the plasmid and host DNA.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140883802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yulia V. Bertsova, Marina V. Serebryakova, Vladimir A. Bogachev, Alexander A. Baykov, Alexander V. Bogachev
{"title":"Acrylate Reductase of an Anaerobic Electron Transport Chain of the Marine Bacterium Shewanella woodyi","authors":"Yulia V. Bertsova, Marina V. Serebryakova, Vladimir A. Bogachev, Alexander A. Baykov, Alexander V. Bogachev","doi":"10.1134/S0006297924040096","DOIUrl":"10.1134/S0006297924040096","url":null,"abstract":"<p>Many microorganisms are capable of anaerobic respiration in the absence of oxygen, by using different organic compounds as terminal acceptors in electron transport chain. We identify here an anaerobic respiratory chain protein responsible for acrylate reduction in the marine bacterium <i>Shewanella woodyi</i>. When the periplasmic proteins of <i>S. woodyi</i> were separated by ion exchange chromatography, acrylate reductase activity copurified with an ArdA protein (Swoo_0275). Heterologous expression of <i>S. woodyi</i> <i>ard</i>A gene (<i>swoo</i>_0275) in <i>Shewanella oneidensis</i> MR-1 cells did not result in the appearance in them of periplasmic acrylate reductase activity, but such activity was detected when the <i>ard</i>A gene was co-expressed with an <i>ard</i>B gene (<i>swoo</i>_0276). Together, these genes encode flavocytochrome <i>c</i> ArdAB, which is thus responsible for acrylate reduction in <i>S. woodyi</i> cells. ArdAB was highly specific for acrylate as substrate and reduced only methacrylate (at a 22-fold lower rate) among a series of other tested 2-enoates. In line with these findings, acrylate and methacrylate induced <i>ard</i>A gene expression in <i>S. woodyi</i> under anaerobic conditions, which was accompanied by the appearance of periplasmic acrylate reductase activity. ArdAB-linked acrylate reduction supports dimethylsulfoniopropionate-dependent anaerobic respiration in <i>S. woodyi</i> and, possibly, other marine bacteria.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140883812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mikhail Yu. Stepanichev, Diana I. Mamedova, Natalia V. Gulyaeva
{"title":"Hippocampus under Pressure: Molecular Mechanisms of Development of Cognitive Impairments in SHR Rats","authors":"Mikhail Yu. Stepanichev, Diana I. Mamedova, Natalia V. Gulyaeva","doi":"10.1134/S0006297924040102","DOIUrl":"10.1134/S0006297924040102","url":null,"abstract":"<p>Data from clinical trials and animal experiments demonstrate relationship between chronic hypertension and development of cognitive impairments. Here, we review structural and biochemical alterations in the hippocampus of SHR rats with genetic hypertension, which are used as a model of essential hypertension and vascular dementia. In addition to hypertension, dysfunction of the hypothalamic-pituitary-adrenal system observed in SHR rats already at an early age may be a key factor of changes in the hippocampus at the structural and molecular levels. Global changes at the body level, such as hypertension and neurohumoral dysfunction, are associated with the development of vascular pathology and impairment of the blood-brain barrier. Changes in multiple biochemical glucocorticoid-dependent processes in the hippocampus, including dysfunction of steroid hormones receptors, impairments of neurotransmitter systems, BDNF deficiency, oxidative stress, and neuroinflammation are accompanied by the structural alterations, such as cellular signs of neuroinflammation micro- and astrogliosis, impairments of neurogenesis in the subgranular neurogenic zone, and neurodegenerative processes at the level of synapses, axons, and dendrites up to the death of neurons. The consequence of this is dysfunction of hippocampus, a key structure of the limbic system necessary for cognitive functions. Taking into account the available results at various levels starting from the body and brain structure (hippocampus) levels to molecular one, we can confirm translational validity of SHR rats for modeling mechanisms of vascular dementia.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140883903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mikhail Raevskiy, Maxim Sorokin, Aleksandra Emelianova, Galina Zakharova, Elena Poddubskaya, Marianna Zolotovskaia, Anton Buzdin
{"title":"Sample-Wise and Gene-Wise Comparisons Confirm a Greater Similarity of RNA and Protein Expression Data at the Level of Molecular Pathways and Suggest an Approach for the Data Quality Check in High-Throughput Expression Databases","authors":"Mikhail Raevskiy, Maxim Sorokin, Aleksandra Emelianova, Galina Zakharova, Elena Poddubskaya, Marianna Zolotovskaia, Anton Buzdin","doi":"10.1134/S0006297924040126","DOIUrl":"10.1134/S0006297924040126","url":null,"abstract":"<p>Identification of genes and molecular pathways with congruent profiles in the proteomic and transcriptomic datasets may result in the discovery of promising transcriptomic biomarkers that would be more relevant to phenotypic changes. In this study, we conducted comparative analysis of 943 paired RNA and proteomic profiles obtained for the same samples of seven human cancer types from The Cancer Genome Atlas (TCGA) and NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) [two major open human cancer proteomic and transcriptomic databases] that included 15,112 protein-coding genes and 1611 molecular pathways. Overall, our findings demonstrated statistically significant improvement of the congruence between RNA and proteomic profiles when performing analysis at the level of molecular pathways rather than at the level of individual gene products. Transition to the molecular pathway level of data analysis increased the correlation to 0.19-0.57 (Pearson) and 0.14-057 (Spearman), or 2-3-fold for some cancer types. Evaluating the gain of the correlation upon transition to the data analysis the pathway level can be used to refine the omics data by identifying outliers that can be excluded from the comparison of RNA and proteomic profiles. We suggest using sample- and gene-wise correlations for individual genes and molecular pathways as a measure of quality of RNA/protein paired molecular data. We also provide a database of human genes, molecular pathways, and samples related to the correlation between RNA and protein products to facilitate an exploration of new cancer transcriptomic biomarkers and molecular mechanisms at different levels of human gene expression.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140884020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evgeniya A. Tikhonova, Pavel G. Georgiev, Oksana G. Maksimenko
{"title":"Functional Role of C-terminal Domains in the MSL2 Protein of Drosophila melanogaster","authors":"Evgeniya A. Tikhonova, Pavel G. Georgiev, Oksana G. Maksimenko","doi":"10.1134/S0006297924040060","DOIUrl":"10.1134/S0006297924040060","url":null,"abstract":"<p>Dosage compensation complex (DCC), which consists of five proteins and two non-coding RNAs <i>roX</i>, specifically binds to the X chromosome in males, providing a higher level of gene expression necessary to compensate for the monosomy of the sex chromosome in male <i>Drosophila</i> compared to the two X chromosomes in females. The MSL2 protein contains the N-terminal RING domain, which acts as an E3 ligase in ubiquitination of proteins and is the only subunit of the complex expressed only in males. Functional role of the two C-terminal domains of the MSL2 protein, enriched with proline (P-domain) and basic amino acids (B-domain), was investigated. As a result, it was shown that the B-domain destabilizes the MSL2 protein, which is associated with the presence of two lysines ubiquitination of which is under control of the RING domain of MSL2. The unstructured proline-rich domain stimulates transcription of the <i>roX2</i> gene, which is necessary for effective formation of the dosage compensation complex.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140883761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nonspecific Interactions in Transcription Regulation and Organization of Transcriptional Condensates","authors":"Anna A. Valyaeva, Eugene V. Sheval","doi":"10.1134/S0006297924040084","DOIUrl":"10.1134/S0006297924040084","url":null,"abstract":"<p>Eukaryotic cells are characterized by a high degree of compartmentalization of their internal contents, which ensures precise and controlled regulation of intracellular processes. During many processes, including different stages of transcription, dynamic membraneless compartments termed biomolecular condensates are formed. Transcription condensates contain various transcription factors and RNA polymerase and are formed by high- and low-specificity interactions between the proteins, DNA, and nearby RNA. This review discusses recent data demonstrating important role of nonspecific multivalent protein–protein and RNA–protein interactions in organization and regulation of transcription.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140883973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cohesin Complex: Structure and Principles of Interaction with DNA","authors":"Arkadiy K. Golov, Alexey A. Gavrilov","doi":"10.1134/S0006297924040011","DOIUrl":"10.1134/S0006297924040011","url":null,"abstract":"<p>Accurate duplication and separation of long linear genomic DNA molecules is associated with a number of purely mechanical problems. SMC complexes are key components of the cellular machinery that ensures decatenation of sister chromosomes and compaction of genomic DNA during division. Cohesin, one of the essential eukaryotic SMC complexes, has a typical ring structure with intersubunit pore through which DNA molecules can be threaded. Capacity of cohesin for such topological entrapment of DNA is crucial for the phenomenon of post-replicative association of sister chromatids better known as cohesion. Recently, it became apparent that cohesin and other SMC complexes are, in fact, motor proteins with a very peculiar movement pattern leading to formation of DNA loops. This specific process has been called loop extrusion. Extrusion underlies multiple functions of cohesin beyond cohesion, but molecular mechanism of the process remains a mystery. In this review, we summarized the data on molecular architecture of cohesin, effect of ATP hydrolysis cycle on this architecture, and known modes of cohesin–DNA interactions. Many of the seemingly disparate facts presented here will probably be incorporated in a unified mechanistic model of loop extrusion in the not-so-distant future.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140886464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Polina A. Khorn, Aleksandra P. Luginina, Vladimir A. Pospelov, Dmitrii E. Dashevsky, Andrey N. Khnykin, Olga V. Moiseeva, Nadezhda A. Safronova, Anatolii S. Belousov, Alexey V. Mishin, Valentin I. Borshchevsky
{"title":"Rational Design of Drugs Targeting G-Protein-Coupled Receptors: A Structural Biology Perspective","authors":"Polina A. Khorn, Aleksandra P. Luginina, Vladimir A. Pospelov, Dmitrii E. Dashevsky, Andrey N. Khnykin, Olga V. Moiseeva, Nadezhda A. Safronova, Anatolii S. Belousov, Alexey V. Mishin, Valentin I. Borshchevsky","doi":"10.1134/S0006297924040138","DOIUrl":"10.1134/S0006297924040138","url":null,"abstract":"<p>G protein-coupled receptors (GPCRs) play a key role in the transduction of extracellular signals to cells and regulation of many biological processes, which makes these membrane proteins one of the most important targets for pharmacological agents. A significant increase in the number of resolved atomic structures of GPCRs has opened the possibility of developing pharmaceuticals targeting these receptors via structure-based drug design (SBDD). SBDD employs information on the structure of receptor–ligand complexes to search for selective ligands without the need for an extensive high-throughput experimental ligand screening and can significantly expand the chemical space for ligand search. In this review, we describe the process of deciphering GPCR structures using X-ray diffraction analysis and cryoelectron microscopy as an important stage in the rational design of drugs targeting this receptor class. Our main goal was to present modern developments and key features of experimental methods used in SBDD of GPCR-targeting agents to a wide range of specialists.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140883970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irina B. Alieva, Anton S. Shakhov, Alexander A. Dayal, Aleksandra S. Churkina, Olga I. Parfenteva, Alexander A. Minin
{"title":"Unique Role of Vimentin in the Intermediate Filament Proteins Family","authors":"Irina B. Alieva, Anton S. Shakhov, Alexander A. Dayal, Aleksandra S. Churkina, Olga I. Parfenteva, Alexander A. Minin","doi":"10.1134/S0006297924040114","DOIUrl":"10.1134/S0006297924040114","url":null,"abstract":"<p>Intermediate filaments (IFs), being traditionally the least studied component of the cytoskeleton, have begun to receive more attention in recent years. IFs are found in different cell types and are specific to them. Accumulated data have shifted the paradigm about the role of IFs as structures that merely provide mechanical strength to the cell. In addition to this role, IFs have been shown to participate in maintaining cell shape and strengthening cell adhesion. The data have also been obtained that point out to the role of IFs in a number of other biological processes, including organization of microtubules and microfilaments, regulation of nuclear structure and activity, cell cycle control, and regulation of signal transduction pathways. They are also actively involved in the regulation of several aspects of intracellular transport. Among the intermediate filament proteins, vimentin is of particular interest for researchers. Vimentin has been shown to be associated with a range of diseases, including cancer, cataracts, Crohn’s disease, rheumatoid arthritis, and HIV. In this review, we focus almost exclusively on vimentin and the currently known functions of vimentin intermediate filaments (VIFs). This is due to the structural features of vimentin, biological functions of its domains, and its involvement in the regulation of a wide range of basic cellular functions, and its role in the development of human diseases. Particular attention in the review will be paid to comparing the role of VIFs with the role of intermediate filaments consisting of other proteins in cell physiology.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140884024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria M. Gridina, Yana K. Stepanchuk, Miroslav A. Nurridinov, Timofey A. Lagunov, Nikita Yu. Torgunakov, Artem A. Shadsky, Anastasia I. Ryabova, Nikolay V. Vasiliev, Sergey V. Vtorushin, Tatyana S. Gerashchenko, Evgeny V. Denisov, Mikhail A. Travin, Maxim A. Korolev, Veniamin S. Fishman
{"title":"Modification of the Hi-C Technology for Molecular Genetic Analysis of Formalin-Fixed Paraffin-Embedded Sections of Tumor Tissues","authors":"Maria M. Gridina, Yana K. Stepanchuk, Miroslav A. Nurridinov, Timofey A. Lagunov, Nikita Yu. Torgunakov, Artem A. Shadsky, Anastasia I. Ryabova, Nikolay V. Vasiliev, Sergey V. Vtorushin, Tatyana S. Gerashchenko, Evgeny V. Denisov, Mikhail A. Travin, Maxim A. Korolev, Veniamin S. Fishman","doi":"10.1134/S0006297924040047","DOIUrl":"10.1134/S0006297924040047","url":null,"abstract":"<p>Molecular genetic analysis of tumor tissues is the most important step towards understanding the mechanisms of cancer development; it is also necessary for the choice of targeted therapy. The Hi-C (high-throughput chromatin conformation capture) technology can be used to detect various types of genomic variants, including balanced chromosomal rearrangements, such as inversions and translocations. We propose a modification of the Hi-C method for the analysis of chromatin contacts in formalin-fixed paraffin-embedded (FFPE) sections of tumor tissues. The developed protocol allows to generate high-quality Hi-C data and detect all types of chromosomal rearrangements. We have analyzed various databases to compile a comprehensive list of translocations that hold clinical importance for the targeted therapy selection. The practical value of molecular genetic testing is its ability to influence the treatment strategies and to provide prognostic insights. Detecting specific chromosomal rearrangements can guide the choice of the targeted therapies, which is a critical aspect of personalized medicine in oncology.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140886320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}