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The heterotrimeric archaeal IF2 orthologue of eukaryotic translation initiation factor 2 consists of the α-subunit, β-subunit and γ-subunit. Previous studies showed that the γ-subunit of aIF2, besides its central role in Met-tRNA i binding, has an additional function: it binds to the 5′-triphosphorylated end of mRNA and protects its 5′-part from degradation. Competition studies with nucleotides and mRNA, as well as structural and kinetic analyses of aIF2γ mutants, strongly implicate the canonical GTP/GDP-binding pocket in binding to the 5′-triphosphate end of mRNAs. The biological implication of these findings is being discussed. [ABSTRACT FROM AUTHOR]

Abstract: Heterotrimeric aIF2αβγ (archaeal homologue of the eukaryotic translation initiation factor 2) in its GTP-bound form delivers Met-tRNAi Met to the small ribosomal subunit. It is known that the heterodimer containing the GTP-bound γ subunit and domain 3 of the α subunit of aIF2 is required for the formation of a stable complex with Met-tRNAi. Here, the crystal structure of an incomplete ternary complex including aIF2αD3γ⋅GDPNP⋅Met-tRNAf Met has been solved at 3.2Å resolution. This structure is in good agreement with biochemical and hydroxyl radical probing data. The analysis of the complex shows that despite the structural similarity of aIF2γ and the bacterial translation elongation factor EF-Tu, their modes of tRNA binding are very different. Remarkably, the recently published 5.0-Å-resolution structure of almost the same ternary initiation complex differs dramatically from the structure presented. Reasons for this discrepancy are discussed. [Copyright &y& Elsevier]