ArticleNucleic acids research2015
Architecture of the eIF2B regulatory subcomplex and its implications for the regulation of guanine nucleotide exchange on eIF2.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response.Antioxidants & redox signaling · 2023Review
- eIF2Bδ blocks the integrated stress response and maintains eIF2B activity and cancer metastasis by overexpression in breast cancer stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulation and function of elF2B in neurological and metabolic disorders.Bioscience reports · 2022Review
- The metaphorical swiss army knife: The multitude and diverse roles of HEAT domains in eukaryotic translation initiation.Nucleic acids research · 2022Review
- GTP binding to translation factor eIF2B stimulates its guanine nucleotide exchange activity.iScience · 2021Article
- Sugar phosphate activation of the stress sensor eIF2B.Nature communications · 2021Article
- Article
- ISRIB Blunts the Integrated Stress Response by Allosterically Antagonising the Inhibitory Effect of Phosphorylated eIF2 on eIF2B.Molecular cell · 2021Article
- Genetic responses of inbred chicken lines illustrate importance of eIF2 family and immune-related genes in resistance to Newcastle disease virus.Scientific reports · 2020Article
- eIF2B and the Integrated Stress Response: A Structural and Mechanistic View.Biochemistry · 2020Article
- The structural basis of translational control by eIF2 phosphorylation.Nature communications · 2019Article
- eIF2B-catalyzed nucleotide exchange and phosphoregulation by the integrated stress response.Science (New York, N.Y.) · 2019Article
- The Prodigal Compound: Return of Ribosyl 1,5-Bisphosphate as an Important Player in Metabolism.Microbiology and molecular biology reviews : MMBR · 2019Review
- The Jigsaw Puzzle of mRNA Translation Initiation in Eukaryotes: A Decade of Structures Unraveling the Mechanics of the Process.Annual review of biophysics · 2018Article
- Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.Science (New York, N.Y.) · 2018Article
- eIF2B Mechanisms of Action and Regulation: A Thermodynamic View.Biochemistry · 2018Article
- Article
- A presumed homologue of the regulatory subunits of eIF2B functions as ribose-1,5-bisphosphate isomerase in Pyrococcus horikoshii OT3.Scientific reports · 2018Article
- Article
- Novel mechanisms of eIF2B action and regulation by eIF2α phosphorylation.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eukaryal translation initiation factor 2B (eIF2B) acts as guanine nucleotide exchange factor (GEF) for eIF2 and forms a central target for pathways regulating global protein synthesis. eIF2B consists of five non-identical subunits (α-ϵ), which assemble into a catalytic subcomplex (γ, ϵ) responsible for the GEF activity, and a regulatory subcomplex (α, β, δ) which regulates the GEF activity under stress conditions. Here, we provide new structural and functional insight into the regulatory subcomplex of eIF2B (eIF2B(RSC)). We report the crystal structures of eIF2Bβ and eIF2Bδ from Chaetomium thermophilum as well as the crystal structure of their tetrameric eIF2B(βδ)2 complex. Combined with mutational and biochemical data, we show that eIF2B(RSC) exists as a hexamer in solution, consisting of two eIF2Bβδ heterodimers and one eIF2Bα2 homodimer, which is homologous to homohexameric ribose 1,5-bisphosphate isomerases. This homology is further substantiated by the finding that eIF2Bα specifically binds AMP and GMP as ligands. Based on our data, we propose a model for eIF2B(RSC) and its interactions with eIF2 that is consistent with previous biochemical and genetic data and provides a framework to better understand eIF2B function, the molecular basis for Gcn(-), Gcd(-) and VWM/CACH mutations and the evolutionary history of the eIF2B complex.
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