title: Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes.
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.
authors.affiliation: University of Grenoble Alpes, UVHCI, F-38000 Grenoble, France CNRS, UVHCI, F-38000 Grenoble, France Unit for Virus Host-Cell Interactions, University of Grenoble Alpes-EMBL-CNRS, 71 avenue des Martyrs, 38042 France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Crepin
authors.affiliation: State Key laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics, 150 Zabolotnogo str., Kiev 03680, Ukraine.
authors.forename: Vyacheslav F
authors.initials: VF
authors.lastname: Shalak
authors.affiliation: State Key laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics, 150 Zabolotnogo str., Kiev 03680, Ukraine European Molecular Biology Laboratory, Grenoble Outstation, 71 avenue des Martyrs, 38042 France.
authors.forename: Anna D
authors.initials: AD
authors.lastname: Yaremchuk
authors.affiliation: State Key laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics, 150 Zabolotnogo str., Kiev 03680, Ukraine.
authors.forename: Dmytro O
authors.initials: DO
authors.lastname: Vlasenko
authors.affiliation: Unit for Virus Host-Cell Interactions, University of Grenoble Alpes-EMBL-CNRS, 71 avenue des Martyrs, 38042 France European Molecular Biology Laboratory, Grenoble Outstation, 71 avenue des Martyrs, 38042 France.
authors.forename: Andrew
authors.initials: A
authors.lastname: McCarthy
authors.affiliation: State Key laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics, 150 Zabolotnogo str., Kiev 03680, Ukraine negrutskii@imbg.org.ua.
authors.forename: Boris S
authors.initials: BS
authors.lastname: Negrutskii
authors.affiliation: State Key laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics, 150 Zabolotnogo str., Kiev 03680, Ukraine.
authors.forename: Michail A
authors.initials: MA
authors.lastname: Tukalo
authors.affiliation: State Key laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics, 150 Zabolotnogo str., Kiev 03680, Ukraine anna.elskaya@yahoo.com.
authors.forename: Anna V
authors.initials: AV
authors.lastname: El'skaya
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006153:Guanosine Diphosphate / Q000737:chemistry* / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D020648:Peptide Elongation Factor 1 / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits
chemical_list: D020648:Peptide Elongation Factor 1; D020033:Protein Isoforms; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D008274:Magnesium