Novosylna O. Structural and functional differences of A1 and proto-oncogenic A2 isoforms of translation elongation factor eEF1A

The thesis is devoted to study of structural and functional differences of two 97.5% homologous isoforms of the translation elongation factor eEF1A. During the work, for the first time it was revealed that spatial organization of eEF1A1 and proto-oncogenic eEF1A2 isoform is different. The eEF1A2 has less hydrophobic surface, is a more compact and less able to dymeryzation.It was shown for the first time that the isoforms eEF1A1 and eEF1A2 interact differently with F-actin, forming actin bundles of various shapes, that may be important for the role of eEF1A2 in carcinogenesis.For the first time found that eEF1A2 isoform, in contrast to eEF1A1 is not able to interact with signaling protein calmodulin, and an original hypothesis was proposed, which explains the reason for tissue-specific expression of the eEF1A2 isoform. For the first time, the absence of the interaction of eEF1A2 isoform with multifunctional protein Sgt1 was revealed and possible significance of the interaction of Sgt1 and eEF1A1 isoform for the antiviral protection system was shown. The original hypothesis was proposed, stating that the tissue-specific A2 isoform may be less important (compared to A1) for Ca2+-modulated cellular control and which may make translation less prone to the conditions of permanent changes in Ca2+ concentrations in muscle, myocardial and neuronal tissues, where A2 is expressed as the only eEF1A isoform.