Conserved sequences in the β subunit of archaeal and eukaryal translation initiation factor 2 (eIF2), absent from eIF5, mediate interaction with eIF2γ

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 (aIF2 beta ). aIF2 beta differs from eIF2 beta 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 eIF2 beta , 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 aIF2 beta , but not in eIF5. We show that the sequence of eIF2 beta homologous to aIF2 beta is sufficient for binding eIF2 gamma , the only subunit with which it interacts, and comprises, at the most, 78 residues. eIF5 does not interact with eIF2 gamma , despite its similarity with eIF2 beta , probably because of a gap in homology in this region. These observations have implications for the evolution of the mechanism of translation initiation.