Laboratory of Protein Biosynthesis
Boris S. Negrutskii
Professor, Dr. Sci. (Mol. Biol.)
Education and Degrees:
1974–1979 Graduate Student, Donetsk National University, Donetsk, Ukraine, M.Sc. (biochemistry)
1979–1983 Postgraduate Student, Department of Translational Mechanisms of Genetic Information (DTMGI), Institute of Molecular Biology and Genetics (IMBG), NASU, Kyiv, Ukraine
1987 Ph.D. (molecular biology), IMBG NASU, Kyiv, Ukraine
1999 Dr.Sci. (molecular biology), IMBG NASU, Kyiv, Ukraine
1983–2000 Engineer, Junior Research Scientist, Research Scientist, Senior Research Scientist, Leader Research Scientist, DTMGI, IMBG NASU, Kyiv, Ukraine
since 2000 Head of the Laboratory of Protein Biosynthesis, DTMGI, IMBG NASU, Kyiv, Ukraine
We investigate the mechanisms of dynamic compartmentalization of the protein synthesis machinery in mammals, molecular composition and cancer-related features of the translation elongation factor 1 (eEF1) complex, spatial structure, expression, post-translational modifications and functions of the normal and proto-oncogenic isoforms of translation elongation factor 1A (eEF1A)
Current research activities:
- The concept of vectorial transfer of tRNA during translation elongation process in mammalian cells has been established. Molecular mechanisms of tRNA channeling have been uncovered
- Spatial structures of A1 and proto-oncogenic A2 isoforms of mammalian eEF1 have been shown to be different despite 97 % homology of their amino acid sequences. Differential interaction of the isoforms with protein partners has been demonstrated which might be important for oncogenecity of A2
- X-ray structure of the proto-oncogenic A2 isoform has been obtained, in collaboration with Department of Protein Synthesis Enzymology, and some peculiariries in the mechanism of GTP/GDP exchange have been reveiled
- Mechanism of overexpression of A2 in tumors has been shown to be related to special microRNAs whose role has been predicted theoretically and proved experimentally
- The components of macromolecular eEF1 complex have been shown to function independently from the complex in human cancer cells and tissues where the subunits may apparently fulfill a non-translational role
- Several grants from National Academy of Sciences of Ukraine, State Fund of Fundamental Research and the Ministry of Education and Science of Ukraine have been obtained. Recently, the laboratory works in frame of State Key Laboratory of Molecular and Cell Biology
- 2012–2014 Project PICS (Projet International de Coopération Scientifique) ”Translation apparatus in cytosol: role in mitochondrial translation and antioxidant homeostasis”
- 2012–2013 Project 5507 STCU (Science and Technology Center in Ukraine) “The A2 isoform of translation elongation factor 1 as a potential oncomarker” supported
- 2011–2014 7th Framework Programme (FP7) FP7-INCO-2011-6, ERA-WIDE Project: “Strengthening cooperation in Molecular Biomedicine between EU and UKRAINE”, COMBIOM (scientific supervisor – Prof. A. Elskaya)
- 2010–2011 Project UKR10/A10 “Structural and biological studies of the eukaryotic elongation factors (eEF) 1B”, supported by BMBF (Bundesministerium für Bildung und Forschung), Germany
- 2009–2012 Program of European science projects GDRI grant “Earlier steps in the development of oncological, autoimmune and neurodegenerative diseases”
- 2009–2011 Program of collaboration between Academy of Sciences of Poland and Ukraine. Project “Investigation of post-translational modifications of the components of human translation machinery during carcinogenesis”
- 2009–2011 PICS (Projet International de Coopération Scientifique) grant “Structural and Functional organization of the translation apparatus in the cytoplasm of human cells”
- 2008–2009 Program of collaboration between NASU and Russian Academy of Sciences. Project “Structural and functional study of the two tissue-specific forms of eukaryotic elongation factor eEF1A”
- 2006–2008 Wellcome Trust N 074742/Z04/Z “Two-faced Janus: mammalian translation elongation factor 1A and its isoforms”
- 2006–2008 INTAS Project 05-7750 “Multisubunit translation elongation factor 1 in health and carcinogenesis”
- 2005–2007 Program of collaboration between Academy of Sciences of Czech Republic and Ukraine, Project “Thermodynamical analysis of the structure of the elongation factors domains in prokaryotes and eukaryotes”
with Ukrainian organizations:
- R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU (Kyiv)
with foreign organizations:
- Laboratory of Enzymology and Structural Biochemistry, CNRS (Gif-sur-Yvette, France)
- Laboratory of Epigenetics of Cancer, CNRS (Gif-sur-Yvette, France)
- University of Liverpool (Liverpool, UK)
- Institute of Protein, RAS (Puschino, Russia)
- Trosiuk TV, Shalak VF, Szczepanowski RH, Negrutskii BS, El'skaya AV. A non-catalytic N-terminal domain negatively influences the nucleotide exchange activity of translation elongation factor 1Bα. FEBS J. 2016 Feb; 283(3):484-97.
- Novosylna O, Doyle A, Vlasenko D, Murphy M, Negrutskii B, El'skaya A.Comparison of the ability of mammalian eEF1A1 and its oncogenic variant eEF1A2 to interact with actin and calmodulin. Biol Chem. 2016 Aug 17. pii: /j/bchm.ahead-of-print/hsz-2016-0172/hsz-2016-0172.xml. doi: 10.1515/hsz-2016-017.
- Novosylna O, Jurewicz E, Pydiura N, Goral A, Filipek A, Negrutskii B, El'skaya A. Translation elongation factor eEF1A1 is a novel partner of a multifunctional protein Sgt1. Biochimie. 2015, Dec;119:137-45.
- Vlasenko DO, Novosylna OV, Negrutskii BS, El'skaya AV. Truncation of the A,A(∗),A' helices segment impairs the actin bundling activity of mammalian eEF1A1.FEBS Lett. 2015;589(11):1187-1193.
- Veremieva M, Kapustian L, Khoruzhenko A, Zakharychev V, Negrutskii B, El'skaya A. Independent overexpression of the subunits of translation elongation factor complex eEF1H in human lung cancer. BMC Cancer. 2014 Dec 3;14:913.
- Shalak V, Vislovukh A, Novosylna O, Khoruzhenko A...Negrutskii B. Characterization of novel peptide-specific antibodies against the translation elongation factor eEF1A2 and their use in eEF1A2 localization in cancer tissues. Biopolymers and Cell.2014;30(6):454-461.
- Trosiuk TV, Liudkovska VV, Shalak VF, Negrutskii1 BS, El’skaya AV. Structural dissection of human translation elongation factor 1Bγ (eEF1Bγ): expression of full-length protein and its truncated forms. Biopolymers and Cell. 2014;30(2):96-106.
- Thibaut Crepin, Shalak VF, Yaremchuk AD, ...El'skaya AV. Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes. Nucleic Acids Research. 2014;42(20):12939-48.
- Vislovukh A, Thaiz Rivera Vargas, Polesskaya A, Groisman I. Role of 3’-untranslated region translational control in cancer development, diagnostics and treatment. World Journal of Biological Chemistry. 2014;5:40–57. doi:10.4331/wjbc.v5.i1.40
- El'skaya AV, Negrutskii BS, Shalak VF, et al. Specific features of protein biosynthesis in higher eukaryotes Biopolym. Cell. 2013; 29(3):177-187 doi: 10.7124/bc.000818
- Vislovukh A, Kratassiouk G, Porto E, Gralievska N, Beldiman C, Pinna G, El'skaya A, HarelBellan A, Negrutskii B, Groisman I. Protooncogenic isoform A2 of eukaryotic translation elongation factor eEF1 is a target of miR663 and miR744. Br J Cancer. 2013 Jun 11;108(11):2304–11. doi: 10.1038/bjc.2013.243
- Negrutskii B, Vlasenko D, El'skaya A. From global phosphoproteo mics to individual proteins: the case of translation elongation factor eEF1A. Expert Rev. Proteomics. 2012; 9(1):71–83. doi: 10.1586/epr.11.71
- Yaremchuk A, Shalak VF, Novosylna OV, et al. Purification, crystallization and preliminary Xray crystallographic analysis of mammalian translation n elongation factor eEF1A2. Acta Cryst. 2012; F68:295–7. doi: 10.1107/S1744309112000243
- Havrylenko S, Legouis R, Negrutskii B, Mirande M. Caenorhabditis elegans evolves a new architecture for the multiaminoacyl tRNA synthetase complex. J. Biol. Chem. 2011; 286:28476–87. doi: 10.1074/jbc.M111.254037
- Veremieva M, Khoruzhenko A, Zaicev S, Negrutskii B, El'skaya A. Unbalanced expression of the translation complex eEF1 subunits in human cardioesophageal carcinoma. Eur. J. Clin. Invest. 2011; 41:269–76. doi: 10.1111/j.1365-2362.2010.02404.x
- Kaminska M, Havrylenko S, Decottignies P, Le Marachal P, Negrutskii B, Mirande M. Dynamic organization of aminoacyl trna synthetase complexes in the cytoplasm of human cells. J. Biol. Chem. 2009; 284: 13746–54. doi: 10.1074/jbc.M900480200
- Kaminska M, Havrylenko S, Decottignies P, et al. Dissection of the structural organization of the aminoacyltRNA synthetase complex. J. Biol. Chem. 2009. 284:6053–60. doi: 10.1074/jbc.M809636200
- Budkevich TV, El'skaya AV, Nierhaus KH. Features of 80S mammalian ribosome and its subunits. Nucleic Acids Res. 2009. 36:4736–44. doi: 10.1093/nar/gkn424
- Negrutskii BS, El'skaya AV. Eukaryotic translation elongation factor 1 alpha: structure, expression, functions, and possible role in aminoacyltRNA channeling. Prog. Nucleic Acid Res. Mol. Biol. 1998; 60:47–78. doi: 10.1016/S0079-6603(08)60889-2