Disease relevance of EIF5B

• Here, we assess the use of IF1/eIF1A and IF2/eIF5B in universal and partial phylogenetic studies by comparison of sequence information from species within all three phylogenetic domains and among closely related strains of Haemophilus parainfluenzae [1].
• This mutant protein behaves in a transdominant manner in transient transfections and leads to a significant decrease in the translation of a reporter gene. hIF2 interacts directly with HIV-1 matrix and Gag in vitro, and the protein complex can be immunoprecipitated from human cells [2].
• The 18-kDa Domain I from the N-terminal region of translation initiation factor IF2 from Escherichia coli was expressed, purified, and structurally characterized using multidimensional NMR methods [3].
• 5-kDa fMet-tRNA binding domain of Bacillus stearothermophilus translation initiation factor IF2, may consist of two subdomains [4].
• For IF2, whose deletion is like that seen in some human heavy chain disease proteins, the most likely explanation is an error of recombination [5].

High impact information on EIF5B

• The IF2 immunoglobulin mutant is a DNA deletion of one coding segment and large sections of the flanking intervening sequences [6].
• The 40S subunit in 48S complexes formed at the initiation codon of mRNA is bound to eukaryotic initiation factor (eIF) 3, eIF1, eIF1A, and an eIF2/GTP/Met-tRNAi(Met) ternary complex and can therefore not join a 60S subunit directly to form an 80S ribosome [7].
• In the absence of eIF1, eIF5-stimulated hydrolysis of eIF2-bound GTP occurred at the same rate in 43S pre-initiation and 48S initiation complexes [7].
• GTP hydrolysis in 43S complexes assembled with eIF1 was much slower than in 43S or 48S complexes assembled without eIF1 [7].
• Translation initiation is promoted by IF1, IF2, and IF3, which mediate base pairing of the initiator tRNA anticodon to the mRNA initiation codon located in the ribosomal P-site [8].

Chemical compound and disease context of EIF5B

• The study was carried out with HT-29 and HCT-116 colorectal and A2780 ovarian carcinoma cells as well as with their irofulven- (HT-29/IF2, HCT-116/IF27) or cisplatin-resistant (A2780/CP70) variants [9].

Biological context of EIF5B

• IF1/eIF1A and IF2/eIF5B, two conserved translation initiation factors are involved in this important step of protein biosynthesis [1].
• Thus, in addition to its role in initiation codon selection during 48S complex formation, eIF1 also participates in maintaining the fidelity of the initiation process at a later stage, hydrolysis of eIF2-bound GTP, by inhibiting premature GTP hydrolysis and by linking establishment of codon-anticodon base-pairing with GTP hydrolysis [7].
• We have confirmed that hIF2 is required for general translation in human cells by generation of a point mutation in the P-loop of the GTP-binding domain [2].
• The C-terminal subdomain (IF2 C-2) contains the entire fMet-tRNA binding site of initiation factor IF2 [4].
• The precise alterations in the protein amino acid sequences of the immunoglobulin heavy chains of spontaneously arisen MOPC 21 mutant clones IF2 and IF1 have been determined [5].

Anatomical context of EIF5B

• IF1 and IF2 have been shown to interact on the ribosome but no binding has been detected for the free factors [10].
• This interaction appears to block hIF2 function, since purified matrix protein inhibits translation in a reticulocyte lysate. hIF2 does not correspond to any of the previously characterized translation initiation factors identified in mammals, but its essential role in translation appears to have been conserved from bacteria to humans [2].
• Expression of translation initiation factor IF2 is regulated during osteoblast differentiation [11].
• RESULTS: Neither DO-7 nor IF2 showed appreciable cross-reactions by Western blot analysis of representative prostate or ovarian cell lines [12].

Associations of EIF5B with chemical compounds

• We show how the occurrence of initiation errors is minimized by (1) recognition of the formyl group by the synergistic action of IF2 and IF1, (2) uniform destabilization of the binding of all tRNAs to the 30S subunit by IF3, and (3) an optimal distance between the Shine-Dalgarno sequence and the initiator codon [13].
• Translational initiation factor 2 (IF2) is a guanine nucleotide-binding protein that can bind guanosine 3',5'-(bis) diphosphate (ppGpp), an alarmone involved in stringent response in bacteria [14].
• IF2 C-2 was further characterized by circular dichroism; by urea-, guanidine hydrochloride-, and temperature-induced unfolding; and by differential scanning calorimetry [4].
• The S. aurantiaca IF2 is distinguished from all other IF2s by a sequence of 160 residues near the N terminus that has an unusual composition, made up essentially of alanine, proline, valine, and glutamic acid [15].
• The low incorporation in comparison to formyl-methionine was not due to the lack of interaction of fluorophore-Met-tRNA(f) with IF-2 [16].

Other interactions of EIF5B

• Here, we have identified the binding interface between human eIF1A and the C-terminal domain of eIF5B by using solution NMR [10].
• The translation machinery in eukaryotes is more complex and accordingly, eIF1A and eIF5B seem to have acquired a number of new functions while also retaining many of the roles of bacterial IF1 and IF2 [10].
• Cloning and characterization of hIF2, a human homologue of bacterial translation initiation factor 2, and its interaction with HIV-1 matrix [2].

Analytical, diagnostic and therapeutic context of EIF5B

• On frozen sections, 100, 65, 35, 73, and 0% of tumors reacted with the CM1, PAb240, PAb1801, IF2, and EA10 antibodies, respectively [17].
• In this work, a PCR assay based on degenerate primers was used to obtain the partial sequence of infB, the gene encoding translation initiation factor 2 (IF2), in 39 clinical isolates of different Enterobacteriaceae [18].
• The rate of evolutionary divergence of initiation factors IF2 and IF3 in various bacterial species determined quantitatively by immunoblotting [19].
• When cloned into an expression vector under the control of the lambda PL promoter, the B. stearothermophilus IF2 gene, reconstituted by ligation of the two separately cloned pieces, could be expressed at high levels in E. coli cells [20].
• Molecular cloning and sequence of the Bacillus stearothermophilus translational initiation factor IF2 gene [20].

References