Press-room / Digest
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Autologous T-Cell-Free Antigen Presentation System Unveils hCMV-Specific NK Cell Response
The scientists from the IBCh RAS proposed the autologous system of the hCMV-derived VMAPRTLFL (LFL) peptide stimulation without T lymphocytes and exogenous cytokines which allows to evaluate NK cell hCMV-specific responses. NK cells of individuals having high anti-hCMV-IgG levels, in contrast to NK cells of hCMV-seronegative and low-positive donors, displayed increased IFNγ production, degranulation and activation levels, and enhanced proliferation upon stimulation with the LFL peptide, presented in HLA-E. LFL-induced NK cell IFNγ production was dependent on PI3K and Ras/Raf/Mek signaling pathways. Transcriptomic profile of LFL-expanded NK cells showed increased adaptive gene expression and metabolic activation. This model may be further exploited for the identification of antigen-specific NK cells. The results are published in the Cells.
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Nanoparticle surface mapping for rational design of drug delivery systems
To achieve control over the formation of a biomolecular corona, it is necessary to control the surface properties of nanoparticles (NPs). Hence, approaches to study the structure and dynamics of NPs surface with high resolution are required. Researchers from IBCh RAS and IC RAS proposed to generate topography maps of NPs surface from MD simulation data, and applied them to analyze the surface structure and dynamics of ligand-containing core–shell NPs. It has been shown that topography maps of NPs surface allow one to evaluate properties important for drug delivery systems. The work was published in the Biomaterials Science journal. Preprint available at ChemRxiv.
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Human RPF1 and ESF1 in Pre-rRNA Processing and Assembly of Pre-Ribosomal Particles: A Functional Study
The scientists from the Department of functioning of living systems IBCh RAS demonstrated the involvement of early (nucleolar) ribosome biogenesis factors RPF1 and ESF1 in the maturation of ribosomal subunits. shRNA-mediated knockdown of these proteins demonstrated a unique change in the pre-rRNAs profile. These proteins in human cells, unlike yeast cells, are not vital, which allows us to argue about the probable rearrangement of the process to maintain the translational activity of cells. Based on the results obtained, authors suggest that the RPF1 and ESF1 proteins perform a structural function and contribute to the correct folding of RNA-protein complexes for further stages of pre-rRNA processing. The results are published in Cells. Learn more
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New Phages Brutus and Scipio: Biology, Evolution, and Phage-Host Interaction
Researchers from the Laboratory of molecular bioengineering IBCh RAS, in collaboration with colleagues from other Russian institutions, have isolated and characterized two new virulent phages of the Obolenskvirus genus, which infect Acinetobacter baumannii, a significant nosocomial pathogen. The phages, named Brutus and Scipio, were capable of infecting A. baumannii strains corresponding to capsular types K116 and K82, respectively. The authors described the biological properties and genomic organization of the phages, and conducted comparative genomic, phylogenetic, and pangenomic analyses. Furthermore, they investigated the enzymatic activity of the tailspike depolymerase encoded in the genome of phage Scipio, marking the first registered virus to infect A. baumannii of the K82 capsular type. The exploration of new representatives within the Obolenskvirus genus enhances our understanding of the diversity of viruses in this taxonomic group and the interaction strategies between Obolenskvirus phages and their host bacteria. This work has been published in the International Journal of Molecular Sciences.
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The rational design of an efficient biocatalyst for the phosphoribosylation of antiviral pyrazine-2- carboxamide derivatives
The antiviral T-1105 and T-705 (Favipiravir) compounds are inactive prodrugs that undergo metabolic transformation into the active form through phosphoribosylation in vivo. The efficiency of this process in human cells is very low, making the production of the phosphoribosylated pyrazine-2-carboxamide derivatives in vitro is a worthy challenge. The researchers from Dep. of Biotechnology of IBCh RAS, along with colleagues from MSU and FSRC “Crystallography and Photonics” RAS report the rational design of an efficient biocatalyst based on the hypoxanthine-guanine phosphoribosyltransferase from T. thermophilus (TthHGPRT). The rational design of TthHGPRT active site has allowed to engineer the D106G/Y155W mutant with a 325-fold increase in the rate of synthesis of T-705-riboside-5’-phosphate and 125-fold – T-1105-riboside-5’-phosphate. The reported results can become the basis for the new technologies of enzymatic production of antiviral compounds. The results are published in ACS Catalysis. Learn more