Summary
Archaeal/eukaryotic initiation factor 2 (a/eIF2) consists of a-, b-, and g-subunits and delivers initiator methionine tRNA (Met-tRNAi) to a small ribosomal subunit in a GTP-dependent manner. The structures of the aIF2bg (archaeal initiation factor 2 bg) heterodimeric complex in the apo and GDP forms were analyzed at 2.8- and 3.4-Å resolution, respectively. The results showed that the N-terminal helix and the central helix-turn-helix domain of the b-subunit bind to the G domain of the g-subunit but are distant from domains 2 and 3, to which the a-subunit and Met-tRNAi bind. This result is consistent with most of the previous analyses of eukaryotic factors, and thus indicates that the binding mode is essentially conserved among a/eIF2. Comparison with the uncomplexed structure showed significant differences between the two forms of the b-subunit, particularly the C-terminal zinc-binding domain, which does not interact with the g-subunit and was suggested previously to be involved in GTP hydrolysis. Furthermore, the switch 1 region in the g-subunit, which is shown to be responsible for Met-tRNAi binding by mutational analysis, is moved away from the nucleotide through the interaction with highly conserved R87 in the b-subunit. These results implicate that conformational change of the b-subunit facilitates GTP hydrolysis by inducing the conformational change of the switch 1 region toward the off state
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