Translation initiation at non-AUG codons mediated by weakened association of eukaryotic initiation factor (eIF) 2 subunits

Hashimoto, Nilce N.; Carnevalli, Larissa S.; Castilho, Beatriz A.

doi:10.1042/bj20020556

Cited by 38 publications

(39 citation statements)

References 20 publications

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“…Indeed, many of the residues involved in this contact are conserved or conservatively substituted in the both subunits of a͞eIF2 ( Fig. 2) and are correlated well with the mutants of the ␤-subunit that show defective association with the ␥-subunit in yeast (17).…”

Section: Resultssupporting

confidence: 52%

Structure of archaeal translational initiation factor 2 βγ–GDP reveals significant conformational change of the β-subunit and switch 1 region

Sokabe

Yao

Sakai

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Archaeal͞eukaryotic initiation factor 2 (a͞eIF2) consists of ␣-, ␤-, and ␥-subunits and delivers initiator methionine tRNA (Met-tRNAi) to a small ribosomal subunit in a GTP-dependent manner. The structures of the aIF2␤␥ (archaeal initiation factor 2 ␤␥) 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 ␤-subunit bind to the G domain of the ␥-subunit but are distant from domains 2 and 3, to which the ␣-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 a͞eIF2. Comparison with the uncomplexed structure showed significant differences between the two forms of the ␤-subunit, particularly the C-terminal zinc-binding domain, which does not interact with the ␥-subunit and was suggested previously to be involved in GTP hydrolysis. Furthermore, the switch 1 region in the ␥-subunit, which is shown to be responsible for Met-tRNA i binding by mutational analysis, is moved away from the nucleotide through the interaction with highly conserved R87 in the ␤-subunit. These results implicate that conformational change of the ␤-subunit facilitates GTP hydrolysis by inducing the conformational change of the switch 1 region toward the off state.initiator methionine tRNA ͉ ribosome

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Section: Resultssupporting

confidence: 52%

Structure of archaeal translational initiation factor 2 βγ–GDP reveals significant conformational change of the β-subunit and switch 1 region

Sokabe

Yao

Sakai

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…The central region, where nb101 and nb131 mutations are located, mediates interactions with eIF2g. The stringency of this interaction is important for the correct selection of the AUG start codon (Thompson et al 2000;Hashimoto et al 2002). This interaction is supported by a crystal structure of P. furiosus aIF2bg in which residues corresponding to the nb101 and nb131 mutations are found in an interface adjacent to the regions that are in close contact with the g-subunit (Sokabe et al 2006).…”

Section: Discussionmentioning

confidence: 55%

Mutations in Caenorhabditis elegans eIF2β Permit Translation Initiation From Non-AUG Start Codons

Zhang

Maduzia

2010

Genetics

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Recognition of the AUG start codon on mRNAs during translation initiation in eukaryotes occurs in a preinitiation complex that includes small ribosomal subunits and multiple translation initiation factors. The complexity of this process and the lack of appropriate tools have prevented its genetic study in multicellular organisms. Here we describe a genetic system in the nematode Caenorhabditis elegans to study how the AUG start codon is selected. We have generated a sensitive reporter assay that allows for the isolation of mutants with reduced fidelity to recognize the AUG start codon. Two mutants were identified to have dominant missense mutations in iftb-1, which encodes the b-subunit of eIF2 (eIF2b). Both mutations occur in a conserved region located outside of the C2-C2 zinc finger domain where yeast SUI3 mutations are localized in Saccharomyces cerevisiae eIF2b. C. elegans iftb-1, as well as mutant eIF2bs carrying the equivalent SUI3 mutations, are able to initiate translation at non-AUG codons that retain two potential base-pairing interactions with the anticodon of the initiator methionyl tRNA. These analyses further support the critical role of eIF2b in start codon selection, and two functional domains within eIF2b are likely involved, one defined by our C. elegans mutants and the other by the yeast SUI3 mutants.

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“…The means by which a protein acquires dual targeting capacity can vary. In some cases, partial relaxation of translation initiation control has occurred [25]. This relaxation might permit occasional initiation upstream to the recognized initiator MET, resulting in two alternative MET initiator sites.…”

Section: Box 1 the Nature Of Organellar Dna Transfers To The Nucleusmentioning

confidence: 99%

Plant organellar protein targeting: a traffic plan still under construction

Mackenzie

2005

Trends in Cell Biology

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It has long been understood that specific features of a protein and its corresponding import apparatus dictate the behavior of mitochondrial proteins in their intracellular targeting behavior. In plants, the process by which proteins are directed to organelles has been influenced uniquely by the introduction to the cell of plastids. Parallel functions carried out within the mitochondrion and plastid permit the sharing of proteins and emergence of mechanisms to facilitate dual-targeting of the nuclear-encoded products to both compartments. These include transcriptional and translational variations, relaxation of translation initiation controls and conditional cellular influences. Details of the dual targeting system are emerging from recent studies, and evidence of variation in protein targeting behavior across plant families and across organisms implies that the system itself is in flux. This trend towards multi-targeting enhances protein versatility across eukaryotes -one means of cellular response to developmental or environmental influence.

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Translation initiation at non-AUG codons mediated by weakened association of eukaryotic initiation factor (eIF) 2 subunits

Cited by 38 publications

References 20 publications

Structure of archaeal translational initiation factor 2 βγ–GDP reveals significant conformational change of the β-subunit and switch 1 region

Structure of archaeal translational initiation factor 2 βγ–GDP reveals significant conformational change of the β-subunit and switch 1 region

Mutations in Caenorhabditis elegans eIF2β Permit Translation Initiation From Non-AUG Start Codons

Plant organellar protein targeting: a traffic plan still under construction

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