Registration Number
0225U004721,
(0120U102238)
, R & D reports
Title
Structural and functional studies of translation elongation factors of higher eukaryotes
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Дослідження молекулярних механізмів дії нових інгібіторів eEF1A із потенційним протипухлинним ефектом
Head
Negrutskyii Borys S., Доктор біологічних наук
Registration Date
17-12-2025
Organization
Institute of Molecular Biology and Genetics of NAS of Ukraine
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The aim of this study is to analyze the spatial organization and function of mammalian translation elongation factor 1 (eEF1A and the multi-protein eEF1B complex). To achieve this, the following tasks are planned. First, to obtain experimental data that will allow us to build atomic models of the spatial organization of the subunits of the eEF1B translation complex and the architecture of the complex as a whole. Second, to conduct experimental studies and to build the model of spatial organization of isoform 1 of elongation factor 1A based on them. Third, to determine the potential functional significance of methylation of lysine residues in the molecule of elongation factor 1A (eEF1A), in particular, to test the hypothesis experimentally that the methylation of some lysine residues in eEF1A may affect the interaction of this protein with partners , such as the subunits of the eEF1B complex, which may reveal the molecular mechanism of the recently discovered effect of eEF1A methylation on oncogenic cell transformation. Fourthly, describe the molecular mechanisms of action of novel eEF1A inhibitors with potential antitumor effect.
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Objects of the study – the human translation factor complex eEF1B, the translation elongation factor eEF1A, the isoforms eEF1A1 and eEF1A2, and the translation elongation factors eEF1Bα, eEF1Bβ, and eEF1Bγ.
The aim of the work is to reveal the spatial organization of translation complexes and their components, and to investigate the potential role of post-translational modifications in the functioning of translation factors.
Research methods – hydrogen–deuterium exchange followed by mass spectrometry, analytical ultracentrifugation, protein mutagenesis, chromatographic purification of individual proteins, analytical gel filtration, a bioluminescence resonance energy transfer system, Western blotting, co-immunoprecipitation, protein co-precipitation, confocal microscopy, mass spectrometry, polymerase chain reaction, molecular-biological DNA techniques, kinetic methods, bioinformatic analysis, molecular modeling, and molecular docking.
The effects of 14 potential inhibitors of the translation elongation factor eEF1A, selected by molecular docking, were studied on six human cancer cell lines. Seven compounds showed inhibitory activity; however, their IC₅₀ values were at least an order of magnitude higher than those of doxorubicin. It was found that some of the compounds alter the intracellular localization of actin and suppress eEF1A-stimulated formation of actin filament bundles, which may indicate a new mechanism of action of eEF1A inhibitors at the cellular level, related to the regulation of F-actin.
Product Description
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Novosylna Oleksandra V.
Hanna V. Yelska
Porublova Larysa V.
Bondarchuk Tetiana V.
Lozhko Dmytro M.
Viacheslav F. Shalak
Oleksandr Y. Tsuvariev
Nazar T. Kolodka
Ihor L. Lysetskyi
Hanna I. Lukianenko
Sofiia V. Hrytsiv
Maryna Kuncova
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2025-12-17
