Institute of
bioorganic chemistry

T cells spot infected and tumour cells by the molecular tags on their surface, and knowing which receptor fits which tag underpins cellular cancer therapies and a new generation of vaccines. A recent independent screen confirmed only about half of the entries in the world’s databases of these matches. Scientists from IBCH RAS and their colleagues have shown how to separate the sound records from the faulty ones: the statistical filter they propose isolates a core of entries that validate experimentally in 81% of cases, against 38% for the rest. Many apparent failures turned out to be annotation errors, not absent recognition. The work is published in Nature Methods. Learn more

Scientists from the Institute of Bioorganic Chemistry of the Russian Academy of Sciences (IBCh RAS) and their colleagues have identified, cloned and characterized the luciferase of the fungus gnat Keroplatus testaceus for the first time. The study strongly suggests that the newly identified enzyme evolved from the storage protein hexamerin, revealing a previously unknown evolutionary pathway for the emergence of bioluminescence in insects. These findings reveal the molecular basis of light emission in dipteran insects and pave the way for the development of new biomedical imaging tools. The study was published in the Journal of Molecular Biology. Learn more

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.