Affinage

EIF5B

Eukaryotic translation initiation factor 5B · UniProt O60841

Length
1220 aa
Mass
138.8 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF5B is a universally conserved translational GTPase that catalyzes ribosomal subunit joining and serves as a kinetic checkpoint gating the transition from translation initiation to elongation. Its chalice-shaped architecture couples GTP hydrolysis in the N-terminal G domain to long-range conformational changes propagated through a rigid α-helical lever (H12) to domain IV at the ribosomal P site, where it cooperates with eIF1A to reorient initiator Met-tRNAi into a subunit-joining-competent conformation and stabilizes it after eIF2 dissociation (PMID:11114334, PMID:35732735, PMID:21335519, PMID:25260592). GTP hydrolysis is triggered by interdomain communication that senses properly positioned initiator tRNA, causing domain IV to disengage from tRNA and enabling eIF5B release from the 80S ribosome; blocking this hydrolysis traps eIF5B on the ribosome and prevents elongation, establishing a fidelity checkpoint (PMID:31900355, PMID:31534220, PMID:12507428). Beyond its canonical role in bulk translation, eIF5B promotes cap-independent and stress-responsive translation of specific mRNAs—including IRES-containing anti-apoptotic transcripts (XIAP, Bcl-xL, cIAP1), PD-L1 under integrated stress response conditions, and developmental targets via interaction with the DEAD-box helicase Vasa—linking it to cell survival, immune evasion, and germ cell development (PMID:32984844, PMID:30670698, PMID:15280213).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Identifying human eIF5B as the functional homolog of bacterial IF2 established that a universally conserved factor promotes initiator Met-tRNA binding to the ribosomal P site across all domains of life.

    Evidence In vivo yeast complementation by archaeal IF2 and in vitro translation assays

    PMID:10200264

    Open questions at the time
    • Precise molecular mechanism of Met-tRNAi delivery was unknown
    • Whether eIF5B had GTPase activity was not yet shown
  2. 2000 High

    Demonstrating that eIF5B possesses ribosome-dependent GTPase activity essential for 40S–60S subunit joining defined the core biochemical function of eIF5B as a GTP-hydrolyzing subunit-joining factor, and discovery of its direct interaction with eIF1A via domain IV identified the first functional partnership in this process.

    Evidence Reconstituted in vitro subunit joining assays, GTPase assays, yeast two-hybrid, co-immunoprecipitation, and in vivo growth assays

    PMID:10659855 PMID:10982835

    Open questions at the time
    • Whether GTP hydrolysis provides mechanical energy or serves a regulatory role was unclear
    • How eIF1A–eIF5B interaction remodels the initiation complex was unknown
  3. 2000 High

    Crystal structures of IF2/eIF5B in multiple nucleotide states revealed a chalice-shaped architecture with a molecular lever that amplifies GTP-induced switch-region changes over 90 Å to domain IV, providing the first structural framework for how the GTPase cycle controls ribosome interactions.

    Evidence X-ray crystallography of free, GDP-bound, and GTP-bound IF2/eIF5B

    PMID:11114334

    Open questions at the time
    • Structure was not ribosome-bound; ribosome-induced conformational changes were not captured
    • The lever mechanism had not been functionally tested by mutagenesis
  4. 2002 High

    Active-site mutagenesis and suppressor genetics resolved that eIF5B GTP hydrolysis acts as a regulatory checkpoint rather than providing mechanical force for subunit joining: switch I mutants blocked hydrolysis but not joining, and suppressors restored translation by reducing ribosome affinity without restoring GTPase activity.

    Evidence D759N XTPase specificity switch in vitro, switch I mutagenesis with intragenic suppressors in yeast

    PMID:12471154 PMID:12507428

    Open questions at the time
    • How GTPase activity gates the transition to elongation in real time was unknown
    • The structural basis of the checkpoint on the ribosome was unresolved
  5. 2004 High

    Discovering that Drosophila Vasa requires direct interaction with eIF5B for translational regulation of gurken mRNA and germ cell formation extended eIF5B's role beyond bulk translation to mRNA-specific developmental control.

    Evidence Site-directed Vasa mutagenesis reducing eIF5B interaction, with female sterility, Gurken loss, and germ cell phenotyping in Drosophila

    PMID:15280213

    Open questions at the time
    • Whether Vasa recruits eIF5B to specific mRNAs directly or indirectly was not resolved
    • Generality to other DEAD-box–eIF5B interactions was untested
  6. 2007 High

    Hydroxyl radical probing mapped all four eIF5B domains on the 80S ribosome, placing domain IV near the peptidyl-transferase center—providing the first ribosome-bound positional framework connecting eIF5B's lever architecture to functional sites.

    Evidence Directed hydroxyl radical cleavage from Fe(II)-EDTA-tethered eIF5B

    PMID:17568775

    Open questions at the time
    • Resolution insufficient to define atomic contacts
    • Conformational dynamics on the ribosome could not be captured by this static method
  7. 2008 High

    Two studies expanded eIF5B's functional network: Puf6p was shown to repress ASH1 mRNA translation by interacting with eIF5B and blocking 48S-to-80S conversion until CK2 phosphorylation relieves repression, while enterovirus 3C proteases were found to cleave eIF5B, linking it to viral translational shutoff.

    Evidence Co-immunoprecipitation and in vitro translation for Puf6p; in vitro 3Cpro cleavage and cell infection for viral cleavage

    PMID:18413716 PMID:18572216

    Open questions at the time
    • Whether Puf6p–eIF5B interaction occurs on specific mRNAs genome-wide was unknown
    • Functional consequences of eIF5B cleavage for host translation during infection were not quantified
  8. 2011 High

    Mutagenesis of helix H12 confirmed its role as a rigid molecular ruler: shortening or flexibilizing H12 reduced subunit joining rates and Met-tRNAi stability in 80S complexes, causing leaky scanning in vivo, directly testing the lever-arm model.

    Evidence Helix length and glycine-substitution mutagenesis with in vitro subunit joining, Met-tRNA binding, and yeast leaky scanning assays

    PMID:21335519

    Open questions at the time
    • How H12 flexibility affects GTPase activation on the ribosome was not examined
    • No structural data of mutant eIF5B on ribosomes
  9. 2014 High

    Multiple advances refined eIF5B's roles: crystal structures revealed a GTP-induced domain-release mechanism generating intrinsic flexibility for catalysis; reconstitution showed eIF5B stabilizes Met-tRNAi in the P site of 40S subunits after eIF2 departure, supporting non-optimal start codon recognition; and eIF5B was identified as a limiting factor whose levels regulate quiescence entry.

    Evidence Six crystal structures with calorimetry; reconstituted 48S assays with mutagenesis; Western blot, polysome profiling, and Xenopus oocyte maturation

    PMID:24686316 PMID:25260592 PMID:25261552

    Open questions at the time
    • The domain-release mechanism had not been visualized on the ribosome
    • How eIF5B levels are regulated during cell cycle transitions was not determined
  10. 2016 Medium

    NMR mapping of multiple dynamic eIF1A–eIF5B interfaces, including an intramolecular eIF5B domain III–IV interaction that gates eIF1A binding, revealed continuous remodeling of these contacts during initiation.

    Evidence NMR spectroscopy and pulldown assays with domain constructs

    PMID:27325746

    Open questions at the time
    • These interactions were not validated in the context of intact ribosomes
    • Functional consequences of disrupting the domain III–IV intramolecular contact in vivo were not tested
  11. 2018 Medium

    Three studies expanded eIF5B's regulatory scope: eIF5 was found to bind eIF5B with ~100-fold higher affinity than eIF1A, potentially coordinating GTPase-regulated initiation steps; eIF5B was shown to be essential for hypoxic translation including ATF4 targets; and eIF5B cooperates with eIF1A and eIF5 in uORF2-mediated ATF4 repression.

    Evidence Competition binding assays; MATRIX proteomics and translatome sequencing; siRNA knockdown with ATF4 translational reporters

    PMID:29298419 PMID:30211544 PMID:30551605

    Open questions at the time
    • The eIF5–eIF5B competition model lacked ribosome-context validation
    • Whether eIF5B's hypoxic role is direct or through general translation reduction was not fully distinguished
    • The mechanistic basis for eIF5B specificity in uORF reinitiation remains unclear
  12. 2019 High

    Single-molecule imaging directly demonstrated that eIF5B has a long residence time on the 80S ribosome after subunit joining and that GTP hydrolysis is required for its release, establishing eIF5B dissociation as a kinetic checkpoint gating elongation; separately, eIF5B was shown to drive IRES-dependent translation of multiple anti-apoptotic mRNAs and NF-κB activation in glioblastoma.

    Evidence Single-molecule fluorescence with GTPase inhibition in purified yeast system; siRNA knockdown with polysome profiling and IRES reporters in glioblastoma cells

    PMID:30670698 PMID:31534220

    Open questions at the time
    • Structural basis of the long-lived 80S-eIF5B state was not yet resolved
    • Whether IRES-dependent translation by eIF5B is a direct or indirect effect was uncertain
  13. 2020 High

    Cryo-EM structures of eIF5B on the 80S ribosome revealed that interdomain communication through Y837 connecting the tRNA-sensing domain IV to the catalytic histidine H480 triggers GTP hydrolysis, and identified a eukaryote-specific fidelity checkpoint; ISR-dependent PD-L1 translation was shown to require eIF5B, linking it to immune evasion.

    Evidence 3.6 Å cryo-EM with mutagenesis; CRISPR screening, siRNA, polysome profiling, and translational reporters in lung cancer cells

    PMID:31900355 PMID:32984844 PMID:33024099

    Open questions at the time
    • The precise structural rearrangement upon GTP hydrolysis in the eukaryotic system was not captured
    • Whether eIF5B directly engages PD-L1 mRNA elements or acts through general ISR pathway changes was not resolved
  14. 2022 High

    Cryo-EM structures of the human initiation complex combined with single-molecule FRET showed that eIF1A and eIF5B cooperate through eukaryote-specific contacts to reorient Met-tRNAi from a scanning-incompatible to a joining-compatible conformation, and bacterial IF2-GDP structures revealed that GDP binding triggers a 35 Å domain relocation releasing tRNA, completing the mechanistic picture of GTPase-gated tRNA handoff.

    Evidence Single-molecule FRET and cryo-EM in reconstituted human system; cryo-EM of P. aeruginosa 70S–IF2-GDP complex

    PMID:35697706 PMID:35732735

    Open questions at the time
    • Full time-resolved structural trajectory of eIF5B conformational changes during human initiation remains unresolved
    • Whether the eukaryotic GDP-induced domain movement mirrors the bacterial one at atomic detail is not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how eIF5B selectively promotes IRES-dependent and ISR-dependent translation of specific mRNAs, what structural features of these mRNAs recruit eIF5B, and how eIF5B levels are dynamically regulated during stress, development, and cell cycle transitions.
  • No structural or biochemical data defining eIF5B–IRES mRNA contacts
  • No mechanism explaining how eIF5B levels are regulated transcriptionally or post-translationally
  • Genome-wide identification of eIF5B-dependent mRNAs under different stress conditions is incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 5 GO:0045182 translation regulator activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005840 ribosome 4 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-5357801 Programmed Cell Death 1
Partners
EIF1AEIF5MET-TRNAIPUF6VASA
Complex memberships
43S/48S pre-initiation complex80S initiation complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 eIF5B (the eukaryotic homolog of bacterial IF2) is essential for joining of 40S and 60S ribosomal subunits to form the 80S ribosome, and possesses a ribosome-dependent GTPase activity that is essential for its function in translation initiation. Reconstituted in vitro translation system, ribosomal subunit joining assay, GTPase assay Nature High 10659855
2000 Crystal structures of IF2/eIF5B in free, GDP-bound, and GTP-bound states reveal a chalice-shaped architecture with G domain, two EF-Tu-type beta barrels, and a novel alpha/beta/alpha sandwich; GTP binding induces conformational changes in the Switch 2 region that are amplified over 90 Å via a molecular lever to domain IV, governing ribosome binding and GTPase function. X-ray crystallography in three nucleotide states Cell High 11114334
2002 eIF5B GTPase activity is required for protein synthesis; mutation of the conserved GTP-binding domain Asp-759 to Asn converts eIF5B to an XTPase, introducing an XTP requirement for subunit joining and translation initiation, demonstrating eIF5B catalyzes a second GTP-dependent step distinct from eIF2. Active-site mutagenesis, in vitro subunit joining assay, in vitro translation Proceedings of the National Academy of Sciences of the United States of America High 12471154
2002 Switch I mutations in eIF5B impair GTP hydrolysis and general translation but not subunit joining per se; intragenic suppressors restoring translation do not restore GTPase activity but reduce ribosome affinity, demonstrating that eIF5B GTP hydrolysis functions as a regulatory checkpoint for 80S assembly rather than providing mechanical force for subunit joining. Yeast genetics, in vitro translation, GTPase assay, ribosome affinity measurements Cell High 12507428
2000 eIF1A and eIF5B interact directly; the eIF1A binding site maps to the C-terminal region (domain IV) of eIF5B; this C-terminal region of eIF5B is critical for yeast growth in vivo and for translation in vitro, and overexpression of eIF1A exacerbates growth defects of C-terminally truncated eIF5B strains. Yeast two-hybrid, co-immunoprecipitation, in vitro binding assay, in vivo growth assay, in vitro translation Molecular and cellular biology High 10982835
2019 eIF5B has a long residence time on the 80S ribosome after ribosomal subunit joining; inhibition of eIF5B GTPase activity after subunit joining prevents eIF5B dissociation and blocks elongation, establishing eIF5B dissociation as a kinetic checkpoint for the transition from initiation to elongation, gated by GTP hydrolysis. Single-molecule fluorescence microscopy in purified yeast translation system Nature High 31534220
2022 Cryo-EM structures combined with single-molecule fluorescence show that eIF1A and eIF5B cooperate to reorient the initiator tRNA from a scanning-incompatible to a subunit-joining-compatible conformation; eukaryote-specific contacts between eIF1A and eIF5B domain IV remodel the initiation complex to orient Met-tRNAi for ribosomal subunit joining in humans. Single-molecule FRET, single-particle cryo-EM, in vitro reconstituted human system Nature High 35732735
2020 CryoEM structure of the 80S–eIF5B–Met-tRNAi complex reveals an unexpected eukaryote-specific fidelity checkpoint implemented by eIF5B together with large ribosomal subunit components immediately before transition into elongation. Cryo-electron microscopy of naturally long-lived eIF5B–80S complex Nature communications High 33024099
2020 Long-range interdomain communication in eIF5B, centered on conserved tyrosine Y837 near the γ-phosphate of GTP, contacts the catalytic histidine H480; this communication transmits the presence of properly delivered initiator tRNA at the P site to the GTPase center to trigger GTP hydrolysis and regulate ribosome binding. Cryo-EM at 3.6 Å with stalled eIF5B–ribosome complex, site-directed mutagenesis, in vitro and in vivo translation assays Proceedings of the National Academy of Sciences of the United States of America High 31900355
2007 Directed hydroxyl radical probing mapped the position of eIF5B on the 80S ribosome: domain 1 is near the GTPase-activating center of the 60S subunit, domain 2 contacts 18S rRNA and rpS23 on the 40S subunit, domain 3 is sandwiched between subunits contacting H95 of 28S rRNA and helix 44 of 18S rRNA, and domain 4 is near the peptidyl-transferase center, contacting rpL10E. Directed hydroxyl radical cleavage of rRNA from tethered Fe(II)–EDTA on eIF5B The EMBO journal High 17568775
2014 eIF5B crystal structures in apo, GDP- and GTP-bound states show that GTP binding induces conformational changes in Switch I and Switch II of the G domain accompanied by rotation of domain II relative to the G domain and release of domain III from Switch 2 contacts, generating intrinsic flexibility (domain release mechanism) required for catalytic function during ribosomal subunit joining. Six high-resolution crystal structures plus thermodynamic nucleotide binding analysis The EMBO journal High 24686316
2011 The α-helix H12 of eIF5B functions as a rigid ruler/lever connecting the GTPase center to domain IV at the P site; shortening H12 by six residues or substituting six consecutive residues with Gly impairs the rate of subunit joining and reduces stability of Met-tRNAi binding in 80S complexes, enhancing ribosome leaky scanning in vivo. Helix length and rigidity mutagenesis, in vitro subunit joining assay, Met-tRNA binding assay, yeast in vivo leaky scanning assay RNA High 21335519
2008 Puf6p (an ASH1 mRNA-binding translational repressor in yeast) interacts with eIF5B (Fun12p) via its PUF domain in an RNA-dependent manner; this interaction is required for Puf6p to block conversion of the 48S complex to the 80S complex during translation initiation; CK2 phosphorylation of Puf6p at Ser31/34/35 relieves this repression. Yeast extract-based in vitro translation, co-immunoprecipitation, phosphorylation assay Genes & development High 18413716
2004 Drosophila Vasa (DEAD-box helicase) interacts directly with eIF5B; site-directed mutations that reduce Vasa–eIF5B interaction cause female sterility, loss of Gurken protein accumulation (indicating translational regulation of grk mRNA), and virtually abolish germ cell formation, demonstrating that eIF5B interaction is essential for Vasa's translational regulatory function during development. Site-directed mutagenesis, genetic analysis, immunostaining, developmental phenotyping Development High 15280213
2020 eIF5B drives ISR-dependent translation of PD-L1 in lung cancer cells; impairment of heme biosynthesis activates the integrated stress response (ISR), allowing bypass of inhibitory uORFs in the PD-L1 5' UTR, and eIF5B is required for this ISR-dependent PD-L1 translation. eIF5B overexpression alone is sufficient to induce PD-L1. CRISPR screening, siRNA knockdown, polysome profiling, translational reporter assays Nature cancer High 32984844
2014 eIF5B and eIF5 together stimulate 48S initiation complex formation during ribosomal scanning; following eIF5-induced GTP hydrolysis by eIF2 and eIF2-GDP dissociation from initiator tRNA, eIF5B stabilizes initiator tRNA in the P site of the 40S subunit, supporting non-optimal start codon recognition. Reconstituted in vitro 48S complex formation assay, mutational analysis of eIF1A and eIF5B Nucleic acids research High 25260592
2018 Human eIF5 interacts with eIF5B via a C-terminal eIF5B-binding motif similar to that in eIF1A; eIF5 competes with eIF1A for eIF5B binding with ~100-fold higher affinity, suggesting eIF5 may help recruit eIF5B to the PIC and that eIF1A displacing eIF5 from eIF5B coordinates the two GTPase-regulated steps of initiation. In vitro binding assays, competition binding, affinity measurements Biochemistry Medium 30211544
2016 Three novel interactions were identified involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A in addition to the known eIF5B-D4/eIF1A-CTT contact; (ii) a dynamic intramolecular interaction within eIF1A between its folded domain and CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4 that interferes with eIF5B/eIF1A contacts. These interactions are continuously rearranged during initiation to remodel the PIC. NMR, pulldown assays, domain-domain binding measurements Nucleic acids research Medium 27325746
2018 eIF5B is an essential component of the cellular hypoxic cap-dependent protein synthesis machinery; MATRIX proteomic analysis demonstrated augmented eIF5B activity in hypoxic translating ribosomes, and global translatome studies showed eIF5B-dependent translation of central carbon metabolism, hypoxic adaptation, and ATF4-mediated stress response pathways. MATRIX (mass spectrometry of active translation factors by ribosome fractionation and isotopic labeling), translatome sequencing, siRNA depletion Cell reports Medium 29298419
2014 eIF5B is upregulated in immature Xenopus oocytes, mouse ES cells, and mammalian cells transitioning to quiescence (G0); increased eIF5B levels lead to increased eIF5B–tRNAiMet complexes; eIF5B is a limiting factor and acts as an antagonist of G0/G0-like states, as its depletion hastens G0 arrest and reduces oocyte maturation. Western blot, polysome profiling, siRNA depletion, overexpression, Xenopus oocyte maturation assay Proceedings of the National Academy of Sciences of the United States of America Medium 25261552
2019 eIF5B depletion sensitizes glioblastoma cells to TRAIL-induced apoptosis through caspases-8, -9, and -7; eIF5B promotes translation of multiple IRES-containing antiapoptotic mRNAs (XIAP, Bcl-xL, cIAP1, c-FLIPS) and promotes NF-κB pathway activation, establishing eIF5B as a node for cap-independent translation of pro-survival proteins under stress. siRNA knockdown, polysome profiling, IRES reporter assay, caspase activation assay Cell death & disease Medium 30670698
2018 eIF5B cooperates with eIF1A and eIF5 to facilitate uORF2-mediated repression of ATF4 translation; siRNA depletion of eIF5B de-represses ATF4 by a mechanism requiring the repressive uORF2, without eIF2α phosphorylation, distinct from eIF2A. siRNA knockdown, polysome profiling, ATF4-luciferase translational reporter, uORF mutagenesis International journal of molecular sciences Medium 30551605
2008 eIF5B is proteolytically cleaved by enterovirus 3C proteases (PV, CVB, HRV 3Cpro) at a single site (VVEQG/VMEQG479 in human eIF5B) that separates the N-terminal domain from the conserved central GTPase and C-terminal domains, potentially contributing to translational shutoff in enterovirus-infected cells. In vitro 3Cpro cleavage of purified native eIF5B, identification of cleavage site by sequencing, cell infection assays Virology Medium 18572216
1999 Human eIF5B (identified as a human IF2 homolog) functions as a translation factor; archaeal IF2 can substitute for yeast eIF5B both in vivo and in vitro, indicating a universally conserved function in facilitating proper binding of initiator Met-tRNA to the ribosomal P site. In vivo complementation assay in yeast, in vitro translation assay Proceedings of the National Academy of Sciences of the United States of America High 10200264
2022 Cryo-EM structures of the 70S initiation complex from P. aeruginosa with compact IF2-GDP show that GDP binding unlocks a cascade of large domain movements propagating from the G domain Switch 2 α-helix to the distal tRNA-binding C2 domain, which relocates 35 Å away from the tRNA, explaining how IF2 releases initiator tRNA for P-site accommodation and gates ribosome transition to elongation. Cryo-electron microscopy of IF2-GDP-bound 70S initiation complex Nature communications High 35697706

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The joining of ribosomal subunits in eukaryotes requires eIF5B. Nature 324 10659855
2000 X-Ray structures of the universal translation initiation factor IF2/eIF5B: conformational changes on GDP and GTP binding. Cell 184 11114334
2006 The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as a metabolic sensor. Proceedings of the National Academy of Sciences of the United States of America 132 16968770
2004 Interaction with eIF5B is essential for Vasa function during development. Development (Cambridge, England) 125 15280213
2000 Chaperone properties of bacterial elongation factor EF-G and initiation factor IF2. The Journal of biological chemistry 119 10625618
1998 Promotion of met-tRNAiMet binding to ribosomes by yIF2, a bacterial IF2 homolog in yeast. Science (New York, N.Y.) 118 9624054
1987 Feedback regulation of rRNA synthesis in Escherichia coli. Requirement for initiation factor IF2. Journal of molecular biology 108 2448483
1984 Sequence of the initiation factor IF2 gene: unusual protein features and homologies with elongation factors. Proceedings of the National Academy of Sciences of the United States of America 108 6096856
2006 The ribosomal stalk binds to translation factors IF2, EF-Tu, EF-G and RF3 via a conserved region of the L12 C-terminal domain. Journal of molecular biology 105 17070545
2002 Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity. Cell 102 12507428
2020 eIF5B drives integrated stress response-dependent translation of PD-L1 in lung cancer. Nature cancer 98 32984844
2002 Initiation factor eIF5B catalyzes second GTP-dependent step in eukaryotic translation initiation. Proceedings of the National Academy of Sciences of the United States of America 89 12471154
1999 Universal conservation in translation initiation revealed by human and archaeal homologs of bacterial translation initiation factor IF2. Proceedings of the National Academy of Sciences of the United States of America 89 10200264
2008 Translation of ASH1 mRNA is repressed by Puf6p-Fun12p/eIF5B interaction and released by CK2 phosphorylation. Genes & development 87 18413716
2000 Physical and functional interaction between the eukaryotic orthologs of prokaryotic translation initiation factors IF1 and IF2. Molecular and cellular biology 77 10982835
2008 Cleavage of eukaryotic initiation factor eIF5B by enterovirus 3C proteases. Virology 71 18572216
1975 Cross-linking of initiation factor IF-2 to Escherichia coli 30 S ribosomal proteins with dimethylsuberimidate. The Journal of biological chemistry 66 805140
2000 The C-terminal subdomain (IF2 C-2) contains the entire fMet-tRNA binding site of initiation factor IF2. The Journal of biological chemistry 60 10644698
2019 eIF5B gates the transition from translation initiation to elongation. Nature 59 31534220
1982 Cloning and mapping of a gene for translational initiation factor IF2 in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 59 6214789
1991 Molecular dissection of translation initiation factor IF2. Evidence for two structural and functional domains. The Journal of biological chemistry 58 1885570
1985 Two translational initiation sites in the infB gene are used to express initiation factor IF2 alpha and IF2 beta in Escherichia coli. The EMBO journal 58 3894004
2022 eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining. Nature 57 35732735
1998 Initiation factors IF1 and IF2 synergistically remove peptidyl-tRNAs with short polypeptides from the P-site of translating Escherichia coli ribosomes. Journal of molecular biology 56 9698545
1987 The protein synthesis initiation factor 2 G-domain. Study of a functionally active C-terminal 65-kilodalton fragment of IF2 from Escherichia coli. Biochemistry 55 2444251
2006 Translation initiation factor IF2 interacts with the 30 S ribosomal subunit via two separate binding sites. Journal of molecular biology 54 16935296
1999 In vitro study of two dominant inhibitory GTPase mutants of Escherichia coli translation initiation factor IF2. Direct evidence that GTP hydrolysis is necessary for factor recycling. The Journal of biological chemistry 54 10037688
2013 Involvement of protein IF2 N domain in ribosomal subunit joining revealed from architecture and function of the full-length initiation factor. Proceedings of the National Academy of Sciences of the United States of America 50 24029017
1983 Organization of the Escherichia coli chromosome around the genes for translation initiation factor IF2 (infB) and a transcription termination factor (nusA). Journal of molecular biology 49 6306257
2007 Position of eukaryotic initiation factor eIF5B on the 80S ribosome mapped by directed hydroxyl radical probing. The EMBO journal 48 17568775
2017 Mutations in eIF5B Confer Thermosensitive and Pleiotropic Phenotypes via Translation Defects in Arabidopsis thaliana. The Plant cell 47 28808135
2003 Ribosomal localization of translation initiation factor IF2. RNA (New York, N.Y.) 47 12869707
1971 A complex between initiation factor IF2, guanosine triphosphate, and fMet-tRNA: an intermediate in initiation complex formation. Proceedings of the National Academy of Sciences of the United States of America 47 4943554
2014 eIF5B employs a novel domain release mechanism to catalyze ribosomal subunit joining. The EMBO journal 44 24686316
1986 Molecular cloning and sequence of the Bacillus stearothermophilus translational initiation factor IF2 gene. Molecular & general genetics : MGG 44 3025563
1992 Both forms of translational initiation factor IF2 (alpha and beta) are required for maximal growth of Escherichia coli. Evidence for two translational initiation codons for IF2 beta. Journal of molecular biology 42 1374802
2010 The ribosomal stalk plays a key role in IF2-mediated association of the ribosomal subunits. Journal of molecular biology 40 20385143
2017 Ribosomal protein L7/L12 is required for GTPase translation factors EF-G, RF3, and IF2 to bind in their GTP state to 70S ribosomes. The FEBS journal 39 28342293
2014 eIF5 and eIF5B together stimulate 48S initiation complex formation during ribosomal scanning. Nucleic acids research 39 25260592
2011 Bacterial ribosome requires multiple L12 dimers for efficient initiation and elongation of protein synthesis involving IF2 and EF-G. Nucleic acids research 39 22102582
2001 Modulation of ribosomal recruitment to 5'-terminal start codons by translation initiation factors IF2 and IF3. FEBS letters 38 11334885
2018 Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B. Cell reports 37 29298419
1995 Mutants of Escherichia coli initiator tRNA defective in initiation. Effects of overproduction of methionyl-tRNA transformylase and the initiation factors IF2 and IF3. The Journal of biological chemistry 36 7538134
1994 Purification procedure for bacterial translational initiation factors IF2 and IF3. Protein expression and purification 35 8054843
2016 eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling. Nucleic acids research 33 27325746
2014 Upregulation of eIF5B controls cell-cycle arrest and specific developmental stages. Proceedings of the National Academy of Sciences of the United States of America 32 25261552
1998 Binding of Escherichia coli initiation factor IF2 to 30S ribosomal subunits: a functional role for the N-terminus of the factor. Biochemical and biophysical research communications 32 9826553
2020 Structural basis for the transition from translation initiation to elongation by an 80S-eIF5B complex. Nature communications 30 33024099
2019 Eukaryotic initiation factor 5B (eIF5B) provides a critical cell survival switch to glioblastoma cells via regulation of apoptosis. Cell death & disease 29 30670698
2018 Complementary charge-based interaction between the ribosomal-stalk protein L7/12 and IF2 is the key to rapid subunit association. Proceedings of the National Academy of Sciences of the United States of America 26 29686090
2016 eIF5B increases ASAP1 expression to promote HCC proliferation and invasion. Oncotarget 25 27694689
1998 A six-domain structural model for Escherichia coli translation initiation factor IF2. Characterisation of twelve surface epitopes. Biochemistry and molecular biology international 25 9861457
2019 Translation initiation factor IF2 contributes to ribosome assembly and maturation during cold adaptation. Nucleic acids research 24 30916323
1991 Superexpression and fast purification of E coli initiation factor IF2. Biochimie 24 1742367
1991 Tandem translation of E. coli initiation factor IF2 beta: purification and characterization in vitro of two active forms. Biochemical and biophysical research communications 23 1764105
2004 The N-terminal domain (IF2N) of bacterial translation initiation factor IF2 is connected to the conserved C-terminal domains by a flexible linker. Protein science : a publication of the Protein Society 21 14691238
2004 The Pseudomonas aeruginosa initiation factor IF-2 is responsible for formylation-independent protein initiation in P. aeruginosa. The Journal of biological chemistry 21 15385567
2001 Remarkable conservation of translation initiation factors: IF1/eIF1A and IF2/eIF5B are universally distributed phylogenetic markers. IUBMB life 20 11699879
2000 Interaction of fMet-tRNA(fMet) with the C-terminal domain of translational initiation factor IF2 from Bacillus stearothermophilus. FEBS letters 20 10767407
2022 Compact IF2 allows initiator tRNA accommodation into the P site and gates the ribosome to elongation. Nature communications 19 35697706
2007 Translation factor IF2 at the interface of transposition and replication by the PriA-PriC pathway. Molecular microbiology 19 18028309
1997 E. coli translation initiation factor IF2--an extremely conserved protein. Comparative sequence analysis of the infB gene in clinical isolates of E. coli. FEBS letters 19 9428651
2021 Established and Emerging Regulatory Roles of Eukaryotic Translation Initiation Factor 5B (eIF5B). Frontiers in genetics 18 34512736
2018 Human eIF5 and eIF1A Compete for Binding to eIF5B. Biochemistry 18 30211544
1992 OmpT proteolysis of E. coli initiation factor IF2. Elimination of a cleavage site by site-directed mutagenesis. Biochemistry international 18 1417895
2020 Long-range interdomain communications in eIF5B regulate GTP hydrolysis and translation initiation. Proceedings of the National Academy of Sciences of the United States of America 17 31900355
2011 Structural integrity of {alpha}-helix H12 in translation initiation factor eIF5B is critical for 80S complex stability. RNA (New York, N.Y.) 17 21335519
2000 Investigation of the translation-initiation factor IF2 gene, infB, as a tool to study the population structure of Streptococcus agalactiae. Microbiology (Reading, England) 17 10878130
1997 Translational initiation factor IF2 from Bacillus stearothermophilus: a spectroscopic and microcalorimetric study of the C-domain. Biochemistry 17 9115993
1994 In vivo study of engineered G-domain mutants of Escherichia coli translation initiation factor IF2. Molecular microbiology 17 8170391
1988 Identification, cloning and sequence of the Streptococcus faecium infB (translational initiation factor IF2) gene. Molecular & general genetics : MGG 17 3063954
2018 Eukaryotic Initiation Factor 5B (eIF5B) Cooperates with eIF1A and eIF5 to Facilitate uORF2-Mediated Repression of ATF4 Translation. International journal of molecular sciences 16 30551605
1990 Characterization of the translational start site for IF2 beta, a short form of Escherichia coli initiation factor IF2. European journal of biochemistry 16 2110058
2009 Ribosomal interaction of Bacillus stearothermophilus translation initiation factor IF2: characterization of the active sites. Journal of molecular biology 15 19917289
2003 Characterization of mutations in the GTP-binding domain of IF2 resulting in cold-sensitive growth of Escherichia coli. Journal of molecular biology 15 12559921
2000 Macromolecular mimicry in translation initiation: a model for the initiation factor IF2 on the ribosome. IUBMB life 15 11327306
2000 Initiation of protein synthesis with fluorophore-Met-tRNA(f) and the involvement of IF-2. Biochimie 14 10727773
2017 IF2 and unique features of initiator tRNAfMet help establish the translational reading frame. RNA biology 13 28914580
2008 Requirements for translation re-initiation in Escherichia coli: roles of initiator tRNA and initiation factors IF2 and IF3. Molecular microbiology 13 18221266
2007 Molecular genetic structure-function analysis of translation initiation factor eIF5B. Methods in enzymology 13 17913624
2024 Methionine-driven YTHDF1 expression facilitates bladder cancer progression by attenuating RIG-I-modulated immune responses and enhancing the eIF5B-PD-L1 axis. Cell death and differentiation 11 39672819
2023 IGF2BP3-induced activation of EIF5B contributes to progression of hepatocellular carcinoma cells. Oncology research 11 37305324
2022 In silico analysis reveals the co-existence of CRISPR-Cas type I-F1 and type I-F2 systems and its association with restricted phage invasion in Acinetobacter baumannii. Frontiers in microbiology 11 36060733
2012 GTPases IF2 and EF-G bind GDP and the SRL RNA in a mutually exclusive manner. Scientific reports 11 23150791
1992 Tandem translation of Bacillus subtilis initiation factor IF2 in E. coli. Over-expression of infBB.su in E. coli and purification of alpha- and beta-forms of IF2B.su. FEBS letters 11 1426242
1990 Purified internal G-domain of translational initiation factor IF-2 displays guanine nucleotide binding properties. Biochemistry 11 2125480
1978 Initiation factor IF-3 and the binary complex between initiation factor IF-2 and formylmethionyl-tRNA are mutually exclusive on the 30-S ribosomal subunit. European journal of biochemistry 11 359327
2008 Translation initiation factor IF1 of Bacillus stearothermophilus and Thermus thermophilus substitute for Escherichia coli IF1 in vivo and in vitro without a direct IF1-IF2 interaction. Molecular microbiology 10 18976282
1997 Identification and purification of translation initiation factor 2 (IF2) from Thermus thermophilus. European journal of biochemistry 10 9030723
1980 The role of the codon and the initiation factor IF-2 in the selection of N-blocked aminoacyl-tRNA for initiation. European journal of biochemistry 10 6989597
2025 A cohort-based multi-omics identifies nuclear translocation of eIF5B /PD-L1/CD44 complex as the target to overcome Osimertinib resistance of ARID1A-deficient lung adenocarcinoma. Experimental hematology & oncology 9 39773749
2022 Essential Role for an Isoform of Escherichia coli Translation Initiation Factor IF2 in Repair of Two-Ended DNA Double-Strand Breaks. Journal of bacteriology 9 35343794
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1984 The rate of evolutionary divergence of initiation factors IF2 and IF3 in various bacterial species determined quantitatively by immunoblotting. Archives of microbiology 9 6084987
2022 Modulation of RecFORQ- and RecA-Mediated Homologous Recombination in Escherichia coli by Isoforms of Translation Initiation Factor IF2. Journal of bacteriology 8 35343793
2021 eIF5B regulates the expression of PD-L1 in prostate cancer cells by interacting with Wig1. BMC cancer 8 34525951
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