Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes |
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| Authors: | Thibaut Crepin Vyacheslav F Shalak Anna D Yaremchuk Dmytro O Vlasenko Andrew McCarthy Boris S Negrutskii Michail A Tukalo Anna V El'skaya |
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| Institution: | 1.University of Grenoble Alpes, UVHCI, F-38000 Grenoble, France;2.CNRS, UVHCI, F-38000 Grenoble, France;3.Unit for Virus Host-Cell Interactions, University of Grenoble Alpes-EMBL-CNRS, 71 avenue des Martyrs, 38042 France;4.State Key laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics, 150 Zabolotnogo str., Kiev 03680, Ukraine;5.European Molecular Biology Laboratory, Grenoble Outstation, 71 avenue des Martyrs, 38042 France |
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| Abstract: | Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon–anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the ‘GTP’- and ‘GDP’-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. |
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