Biology subjects

Gorshkov, A. N.

Publications and source records attributed to Gorshkov, A. N..

3 recordsLinked to original sources

bioRxiv2023

How the immune mousetrap works: structural evidence for the immunomodulatory action of a peptide from influenza NS1 protein

One of the critical stages of the T-cell immune response is the dimerization of the intramembrane domains of T-cell receptors (TCR). Structural similarities between the immunosuppressive domains of viral proteins and the transmembrane domains of TCR have led several authors to hypothesize the mechanism of immune response suppression by highly pathogenic viruses: viral proteins embed themselves in the membrane and act on the intramembrane domain of the TCRalpha subunit, hindering its functional oligomerization. It has also been suggested that this mechanism is used by influenza A virus in NS1-mediated immunosuppression. We have shown that the peptide corresponding to the primary structure of the potential immunosuppressive domain of NS1 protein (G51) can reduce concanavalin A-induced proliferation of PBMC cells, as well as in vitro, G51 can affect the oligomerization of the core peptide corresponding to the intramembrane domain of TCR, using AFM and small-angle neutron scattering. The results obtained using in cellulo and in vitro model systems suggest the presence of functional interaction between the NS1 fragment and the intramembrane domain of the TCR alpha subunit. We have proposed a possible scheme for such interaction obtained by computer modeling. This suggests the existence of another NS1-mediated mechanism of immunosuppression in influenza. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=73 SRC="FIGDIR/small/573289v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@12b4ce4org.highwire.dtl.DTLVardef@1c53557org.highwire.dtl.DTLVardef@30f519org.highwire.dtl.DTLVardef@2b71bf_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Inside and outside of virus-like particles HBc and HBc/4M2e: a comprehensive study of the structure

The structure of the core particles of the hepatitis B virus core antigen (HBc) with the insertion of four external domains of the influenza A M2 protein (HBc/4M2e) have been studied using a combination of molecular modeling and cryogenic electron microscopy (cryo-EM). It has also been shown that synthesis of particles occurs inside bacterial cells, but despite the big inner volume of the core shell particle, purified HBc/4M2e do not contain detectable amounts of bacterial proteins. It has been shown that a fragment of the M2e is prone to the formation of amyloid-like fibrils. However, as a part of HBc immunodominant loop M2e domains as repeats, does not exhibit a tendency to aggregation. Full-atom HBc-4M2E model with 3A resolution was obtained by molecular modeling methods based on cryo-EM data.

biophysics↗

bioRxiv2020

THE MATRIX IS EVERYWHERE: CACO3 BIOMINERALIZATION BY THE BACILLUS LICHENIFORMIS PLANKTONIC CELLS

To date, the mechanisms of CaCO3 nucleus formation and crystal growth induced by bacterial cells still remain debatable. Here, an insight on the role of planktonic cells of Bacillus licheniformis DSMZ 8782 in the biomineralization is presented. We showed that during 14-days bacterial growth in a liquid urea/Ca2+-containing medium the transformation of CaCO3 polymorphs followed the classical pathway "ACC-vaterite-calcite/aragonite". By microscopic techniques, we detected the formation of extracellular matrix (ECM) around the cells at the stage of exponential growth and appearance of electron-dense inclusions at 24 h after the inoculation. The cells formed filaments and created a network, the nodes of which served as sites for further crystal growth. The ECM formation accompanied with the expression of proteins required for biofilm formation, the aldehyde/alcohol dehydrogenase, stress-associated Clp family proteins, and a porin family protein (ompA ortholog) associated with bacterial extracellular vesicles. We demonstrated that urea and CaCl2 acted as denaturing agents causing matrix formation in addition to their traditional role as a source of carbonate and Ca2+ ions. We showed that CaCO3 nucleation occured inside B. licheniformis cells and further crystal growth and polymorphic transformations took place in the extracellular matrix without attaching to the cell surface. The spatial arrangement of the cells was important for the active crystal growth and dependent on environmental factors. The extracellular matrix played a double role being formed as a stress response and providing a favorable microenvironment for biomineralization (a high concentration of ions necessary for CaCO3 crystal aggregation, fixation and stabilization).

microbiology↗