Open AccessStructure of archaeal translational initiation factor 2 βγ–GDP reveals significant conformational change of the β-subunit and switch 1 region
Author(s) -
Masaaki Sokabe,
Min Yao,
Naoki Sakai,
S. Toya,
Isao Tanaka
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0604165103
Subject(s) - protein subunit , transfer rna , conformational change , gtp' , biology , eukaryotic large ribosomal subunit , eukaryotic small ribosomal subunit , eif2 , specificity factor , biochemistry , ribosome , rna , enzyme , rna polymerase , gene
Archaeal/eukaryotic initiation factor 2 (a/eIF2) consists of α-, β-, and γ-subunits and delivers initiator methionine tRNA (Met-tRNAi ) to a small ribosomal subunit in a GTP-dependent manner. The structures of the aIF2βγ (archaeal initiation factor 2 βγ) 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 β-subunit bind to the G domain of the γ-subunit but are distant from domains 2 and 3, to which the α-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 β-subunit, particularly the C-terminal zinc-binding domain, which does not interact with the γ-subunit and was suggested previously to be involved in GTP hydrolysis. Furthermore, the switch 1 region in the γ-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 β-subunit. These results implicate that conformational change of the β-subunit facilitates GTP hydrolysis by inducing the conformational change of the switch 1 region toward the off state.