title: A non-catalytic N-terminal domain negatively influences the nucleotide exchange activity of translation elongation factor 1Bα.
abstract: Eukaryotic translation elongation factor 1Bα (eEF1Bα) is a functional homolog of the bacterial factor EF-Ts, and is a component of the macromolecular eEF1B complex. eEF1Bα functions as a catalyst of guanine nucleotide exchange on translation elongation factor 1A (eEF1A). The C-terminal domain of eEF1Bα is necessary and sufficient for its catalytic activity, whereas the N-terminal domain interacts with eukaryotic translation elongation factor 1Bγ (eEF1Bγ) to form a tight complex. However, eEF1Bγ has been shown to enhance the catalytic activity of eEF1Bα attributed to the C-terminal domain of eEF1Bα. This suggests that the N-terminal domain of eEF1Bα may in some way influence the guanine nucleotide exchange process. We have shown that full-length recombinant eEF1Bα and its truncated forms are non-globular proteins with elongated shapes. Truncation of the N-terminal domain of eEF1Bα, which is dispensable for catalytic activity, resulted in acceleration of the rate of guanine nucleotide exchange on eEF1A compared to full-length eEF1Bα. A similar effect on the catalytic activity of eEF1Bα was observed after its interaction with eEF1Bγ. We suggest that the non-catalytic N-terminal domain of eEF1Bα may interfere with eEF1A binding to the C-terminal catalytic domain, resulting in a decrease in the overall rate of the guanine nucleotide exchange reaction. Formation of a tight complex between the eEF1Bγ and eEF1Bα N-terminal domains abolishes this inhibitory effect.
authors.affiliation: State Key Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Tetiana V
authors.initials: TV
authors.lastname: Trosiuk
authors.affiliation: State Key Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Vyacheslav F
authors.initials: VF
authors.lastname: Shalak
authors.affiliation: International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Roman H
authors.initials: RH
authors.lastname: Szczepanowski
authors.affiliation: State Key Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Boris S
authors.initials: BS
authors.lastname: Negrutskii
authors.affiliation: State Key Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Anna V
authors.initials: AV
authors.lastname: El'skaya
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000737:chemistry* / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D009711:Nucleotides; D020648:Peptide Elongation Factor 1; D020033:Protein Isoforms; D011994:Recombinant Proteins; C000599473:eEF1B-alpha protein, human
keywords: eukaryotic translation: guanine nucleotide exchange; non-globular proteins; protein-protein interactions; translation elongation factor 1