title: Conserved sequences in the beta subunit of archaeal and eukaryal translation initiation factor 2 (eIF2), absent from eIF5, mediate interaction with eIF2gamma.
abstract: The eukaryotic translation initiation factor 2 (eIF2) binds the methionyl-initiator tRNA in a GTP-dependent mode. This complex associates with the 40 S ribosomal particle, which then, with the aid of other factors, binds to the 5' end of the mRNA and migrates to the first AUG codon, where eIF5 promotes GTP hydrolysis, followed by the formation of the 80 S ribosome. Here we provide a comparative sequence analysis of the beta subunit of eIF2 and its archaeal counterpart (aIF2beta). aIF2beta differs from eIF2beta in not possessing an N-terminal extension implicated in binding RNA, eIF5 and eIF2B. The remaining sequences are highly conserved, and are shared with eIF5. Previously isolated mutations in the yeast eIF2beta, which allow initiation of translation at UUG codons due to the uncovering of an intrinsic GTPase activity in eIF2, involve residues that are conserved in aIF2beta, but not in eIF5. We show that the sequence of eIF2beta homologous to aIF2beta is sufficient for binding eIF2gamma, the only subunit with which it interacts, and comprises, at the most, 78 residues. eIF5 does not interact with eIF2gamma, despite its similarity with eIF2beta, probably because of a gap in homology in this region. These observations have implications for the evolution of the mechanism of translation initiation.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatú, 862, São Paulo, 04023-062, Brasil.
authors.forename: G M
authors.initials: GM
authors.lastname: Thompson
authors.forename: E
authors.initials: E
authors.lastname: Pacheco
authors.forename: E O
authors.initials: EO
authors.lastname: Melo
authors.forename: B A
authors.initials: BA
authors.lastname: Castilho
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics; D005057:Eukaryotic Cells; D015852:Eukaryotic Initiation Factor-2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D040061:Eukaryotic Initiation Factor-5; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D020798:Two-Hybrid System Techniques
chemical_list: D019843:Archaeal Proteins; D015852:Eukaryotic Initiation Factor-2; D040061:Eukaryotic Initiation Factor-5; D005656:Fungal Proteins; D010448:Peptide Initiation Factors