Biology subjects

Tsvetkov, V. B.

Publications and source records attributed to Tsvetkov, V. B..

4 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

Modeling of possible quadruplexes and i-motifs formed during DNA contacts: strategy, classification, most probable shapes, origami based on quadruplexes.

A strategy for creating 3D models of non-canonical forms of DNA and RNA is proposed in this research. Through this strategy, models of all possible forms of non-canonical structures created by contacts of single-stranded DNA with sequence (G3T)nG3 and/or duplexes with (G3T)nG3 and (C3A)nC3 fragments were built and tested by MD. In particular, models of stacks formed from right and left twisted quadruplexes; the structure resembling the Holliday structure, with the hole, on the border of which the quadruplex (G4) and the i-motif (IM) were located opposite each other; layers formed from G4s grids were constructed. The most probable of these non-canonical forms arising from contacts of duplexes with (G3T)nG3 for n=1,3,5 were determined by estimating the contributions to the free energy.

biochemistry↗

bioRxiv2022

Red light-emitting short Mango-based system enables tracking a mycobacterial small noncoding RNA in infected macrophages

Progress in the studies of RNA metabolism and function relies largely on molecular imaging systems, including those comprising a fluorogenic dye and an aptamer-based fluorescence-activating tag. G4 aptamers of Mango family, typically combined with a duplex/hairpin scaffold, activate fluorescence of a green-emitting dye TO1-biotin and hold great promise for intracellular RNA tracking. Here, we report a new Mango-based imaging platform. Its key advantages are tunability of spectral properties and applicability for visualization of small RNA molecules that require minimal tag size. The former advantage is due to an expanded (green-to-red-emitting) palette of TO1-inspired fluorogenic dyes, and the latter is ensured by the truncated duplex scaffold. To illustrate applicability of the improved platform, we tagged Mycobacterium tuberculosis sncRNA with the shortened aptamer-scaffold tag and visualized it in bacteria and bacteria-infected macrophages using the new red light-emitting Mango-activated dye.

synthetic biology↗

bioRxiv2018

A double-edged sword: supramolecular complexes of triazavirine display multicenter binding effects which influence aggregate formation

Triazavirine (TZV), a small molecule with a broad spectrum of antiviral activity, shows a tendency to induce the aggregation of melittin (MLT), a cationic membrane-disrupting peptide from the poison of the European bee. In MLT:TZV mixtures, high molecular weight precipitates form once a critical MLT:TZV ratio has been exceeded. Molecular dynamics simulation of MLT-TZV interactions, followed by molecular docking, led us to the hypothesis of multicenter binding of TZV supramolecular complexes to MLT.

biophysics↗