Biology subjects

Egorov, V.

Publications and source records attributed to Egorov, V..

5 recordsLinked to original sources

bioRxiv2023

Peptide fibrils as vaccine: a proof of concept

The potential of amyloid-like fibrils formed by peptides as vaccine candidates was investigated using a fragment of the Ebola virus glycoprotein. Peptide in fibrillar form were found to induce an immune response to the full-length protein without causing cellular toxicity or significant changes in hematological studies. The ability of the studied peptide fragment to oligomerize and form amyloid-like fibrils and intermediates suggests potential implications for the viruss mechanisms of action on cells, particularly those of the immune system. Additionally, if native GP2 epitopes are retained in the peptide fibrils, they may serve as effective immunization agents due to their autoadjuvant properties; however, it is important to consider the possibility of cross-reactivity with human proteins. These findings provide valuable insights into the potential use of amyloid-forming peptide as vaccine candidates and highlight the need for further research into their immunogenic and adjuvant properties.

biophysics↗

bioRxiv2020

Old Dog, New Tricks: Influenza A Virus NS1 and In Vitro Fibrillogenesis

The influenza NS1 protein is involved in suppression of the host immune response. Recently, there is growing evidence that prion-like protein aggregation plays an important role in cellular signaling and immune responses. In this work, we obtained a recombinant, influenza A NS1 protein and showed that it is able to form amyloid-like fibrils in vitro. Using proteolysis and subsequent mass spectrometry, we showed that regions resistant to protease hydrolysis highly differ between the native NS1 form (NS1-N) and fibrillar form (NS1-F); this indicates that significant structural changes occur during fibril formation. The discovery of the ability of NS1 to form amyloid-like fibrils may be relevant to uncovering relationships between influenza A infection and modulation of the immune response.

molecular biology↗

bioRxiv2019

Cold and distant: structural features of the nucleoprotein complex of a cold-adapted influenza A virus strain

Two influenza A nucleoprotein variants (wt: G102R; and mutant: G102R and E292G) were studied with regard to macro-molecular interactions in oligomeric form (24-mers). The E292G mutation has been previously shown to provide cold adaptation. Molecular dynamics simulations of these complexes and trajectory analysis showed that the most significant difference between the obtained models was distance differences between nucleoprotein complex strands. Influenza virus nucleoprotein complexes were isolated from strains bearing the corresponding NP amino acid substitutions. The isolated complexes were characterized by transmission electron microscopy and differential scanning fluorimetry (DSF). Presence of the E292G substitution was shown by DSF to affect nucleoprotein complex melting temperature. In the filament interface peptide model, it was shown that the peptide corresponding in primary structure to the wild-type NP (SGYDFEREGYS, wild type peptide) is prone to temperature-dependent self-association, unlike the peptide carrying the substitution corresponding to E292G (SGYDFGREGYS, mutant peptide). It was also shown that the SGYDFEREGYS peptide (wt) is capable of interacting with a recombinant full-size monomeric nucleoprotein (with primary structure corresponding to wild type); this interactions equilibrium dissociation constant is five orders of magnitude lower than for the SGYDFGREGYS peptide. Using small-angle neutron scattering (SANS), the supramolecular structures of isolated complexes of these proteins was studied at temperatures of 15, 32, and 37{degrees}C. SANS data show that the structures of the studied complexes (mutant or normal proteins with RNA) at elevated temperature differ from the rod-like particle model and react differently to temperature changes. The data suggest that the mechanism behind cold adaptation with E292G is associated with a weakening of the interaction between strands of the ribonucleoprotein complex and, as a result, the appearance of inter-chain interface flexibility necessary for complex function at low temperature.

biophysics↗

bioRxiv2019

Effect of Alpha-Lactalbumin and Lactoferrin Oleic Acid Complexes on Chromatin Structural Organization

This work focuses on the study of multimeric alpha-lactalbumin oleic acid and lactoferrin oleic acid complexes. The purpose of the research is to study possible mechanisms involved in their pro-apoptotic activities, as seen in some tumor cell cultures. Complexes featuring oleic acid (OA) with human alpha-lactalbumin (hAl) or with bovine alpha-lactalbumin (bAl), and human lactoferrin (hLf) were investigated using small-angle neutron scattering (SANS). It was shown that while alpha-lactalbumin protein complexes were formed on the surface of polydisperse OA micelles, the lactoferrin complexes comprised a monodisperse system of nanoscale particles. Both hAl and hLf complexes appeared to interact with the chromatin of isolated nuclei affecting chromatin structural organization. The possible roles of these processes in the specific anti-tumor activity of these complexes are discussed.

biophysics↗

bioRxiv2017

Triazavirine supramolecular complexes as modifiers of the peptide oligomeric structure

In this study we present molecular dynamics simulations of the antiviral drug triazavirine, that affects formation of amyloid-like fibrils of the model peptide (SI). According to our simulations, triazavirine is able to form linear supramolecular structures which can act as shields and prevent interactions between SI monomers. This model, as validated by simulations, provides an adequate explanation of triazavirines mechanism of action as it pertains to SI peptide fibril formation.

biophysics↗