Institute of
bioorganic chemistry

Adaptive NK cells coexpressing KIR and NKG2C receptors are promising antitumor effectors. A team of researchers from the Institute of Bioorganic Chemistry used stimulation with a cytomegalovirus peptide presented within the HLA-E molecule to expand such effectors in vitro, and revealed the dependence of the accumulation of adaptive NK cells possessing high HLA-E-directed cytotoxicity on the NK cell phenotype ex vivo.These findings are of interest for the therapeutic use of NK cells, and also contribute to a better understanding of virus-mediated modulation of NK cell population diversity. The study is supported by RSF grant 26-15-00648 and published in the International Journal of Molecular Science.

Researchers from the IBCh RAS, in collaboration with colleagues from the IGB RAS and the Gamaleya Center, have developed a novel strategy for anti-SARS-Cov-2 nanobodies modification. The potential to enhance the activity of three VHH antibodies specific to the receptor-binding domain of the SARS-CoV-2 spike protein were investigated. Tetramerization of nanobodies and their fusion with the Fc domain substantially increased the affinity of these molecules for the viral protein, while conjugation with the small-molecule antiviral compound ARVI11 resulted in a pronounced enhancement of neutralizing activity compared to the original monomeric proteins. Nanobody multimerization and targeted delivery of antiviral molecules opens new avenues for the development of new antiviral agents. The results are published in ACS Omega.

Theoretically, any nucleotide sequence can be translated in three reading frames, resulting in three different polypeptides. However, so far, only dual coding natural mRNAs have been found. A group of researchers from IBHh, University College Cork and other institutes have discovered a unique case of triple coding in the SRD5A1 gene. In this gene, translation initiation occurs on three closely spaced AUG codons within three reading frames. Depending on the splicing, translation from one of the three start codons leads to the synthesis of a protein with a catalytic domain. The unusual architecture of the gene makes it possible not to lose the expression of a protein with a catalytic domain in case of indel mutations. This work is published in Genome Biology.

Researchers from the Laboratory of Neuroreceptors and Neuroregulators IBCh RAS have advanced the use of concatemeric constructs to investigate acid-sensing ion channel 3 (ASIC3), a promising target for pain therapy. By assembling rat and human ASIC3 subunits in certain combinations and orders, the research team established that functional properties of resulted channels are determined not only by the subunit composition but by the genes sequence into the concatemer. Homomeric concatemers closely reproduced the properties of native ASIC3 channels, whereas exchange of a single subunit markedly altered proton sensitivity and channel gating. The study provides new insight into species-specific ASIC3 function and offers a valuable experimental framework for interpreting rodent studies in the context of human physiology. The results are published in the Journal of Physiology and Biochemistry.

Researchers from IBCh RAS, as part of an international collaboration, have elucidated how the endogenous polyamine spermine blocks the calcium-selective TRPV6 ion channel, which is hyperactive in prostate, breast, and pancreatic cancers. Using a combination of cryo-EM, molecular modeling, electrophysiology, and site-directed mutagenesis, it was shown that spermine enters the open TRPV6 pore in a stepwise manner and physically occludes it like a “plug”. These findings advance our understanding of calcium homeostasis regulation under both physiological conditions and in cancer. The study was supported by the Russian Ministry of Science and Higher Education (computational modeling) and published in Nature Communications. Learn more