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Registration Number

0225U004214, (0124U004173) , R & D reports

Title

Highly homologous paralogs of translation elongation factor 1A. Structural studies to understand functional differences.

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Дослідження молекулярної і структурної динаміки eEF1A1 і eEF1A2.

Head

Negrutskii Borys S., д.б.н.

Registration Date

26-11-2025

Organization

Institute of Molecular Biology and Genetics of NAS of Ukraine

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The aim of the project is to define the structural organization of eEF1A1 and eEF1A2 in solution by creating their high-quality, experimentally validated structural models. We aim to precisely identify the structurally dynamic regions in both proteins, find out their differences, and show possible functional consequences of these differences for protein synthesis.

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The project is dedicated to studying the dynamics of the spatial organization of two very similar proteins, eEF1A1 and eEF1A2, which are key factors involved in protein chain synthesis by mammalian ribosomes. Mutations in eEF1A2 lead to neuropathic and cardiological diseases. In contrast, only eEF1A1 is involved in the development of diseases caused by certain RNA-containing viruses, such as COVID-19. The reason for the mutually exclusive involvement of these proteins in the progression of different diseases remains unclear. We believe that this is related to their different post-translational functions, which are enabled by their ability to interact with various partner proteins. The difference in protein-protein interactions may be due to the distinct spatial organization of eEF1A1 and eEF1A2, the study of which is the focus of this project.The goal of the scientific project is to uncover the spatial organization of eEF1A1 and eEF1A2 in solution, to accurately identify sites with different structural dynamics, and to reveal the potential functional consequences of the differences in the spatial structures of these proteins. An additional influencing factor is the post-translational modifications of these proteins, in particular, the methylation of lysine residues. The methylation sites of these proteins are well known, but the functional role of this modification in translation factors is not yet fully understood. Given that methylated lysines are located on the surface of the protein, we hypothesize that this modification may potentially influence interactions with partner molecules, particularly with other components of the protein synthesis system in cells. In 2025, using molecular dynamics simulations in the microsecond range, significant structural differences between the eEF1A1 and eEF1A2 paralogs were shown, and the amino acid residues responsible for these differences were identified. Using HDX-MS, structural regions of these proteins were experimentally

Product Description

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Novosylna Oleksandra V.
Porublova Larysa V.
Tetiana V. Bondarchuk
Viacheslav F. Shalak

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2025-11-26