title: eIF2B: recent structural and functional insights into a key regulator of translation.
abstract: The eukaryotic translation initiation factor (eIF) eIF2B is a key regulator of mRNA translation, being the guanine nt exchange factor (GEF) responsible for the recycling of the heterotrimeric G-protein, eIF2, which is required to allow translation initiation to occur. Unusually for a GEF, eIF2B is a multi-subunit protein, comprising five different subunits termed α through ε in order of increasing size. eIF2B is subject to tight regulation in the cell and may also serve additional functions. Here we review recent insights into the subunit organization of the mammalian eIF2B complex, gained both from structural studies of the complex and from studies of mutations of eIF2B that result in the neurological disorder leukoencephalopathy with vanishing white matter (VWM). We will also discuss recent data from yeast demonstrating a novel function of the eIF2B complex key for translational regulation.
authors.affiliation: University of Southampton, Centre for Biological Sciences, Life Sciences Building 85, Highfield Campus, Southampton SO17 1BJ, U.K. Trafalgar School, London Road, Hilsea, Portsmouth, Hampshire, PO2 9RJ, U.K. nwortham@trafalgarschool.org.uk.
authors.forename: Noel C
authors.initials: NC
authors.lastname: Wortham
authors.affiliation: University of Southampton, Centre for Biological Sciences, Life Sciences Building 85, Highfield Campus, Southampton SO17 1BJ, U.K. South Australian Health and Medical Research Institute, North Terrace, Adelaide SA 5000, Australia.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Proud
mesh_terms: D000818:Animals; D020717:Eukaryotic Initiation Factor-2B / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D014176:Protein Biosynthesis / Q000235:genetics*; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D020717:Eukaryotic Initiation Factor-2B; D021122:Protein Subunits
keywords: eukaryotic initiation factor 2B (eIF2B); integrated stress response; integrated stress response inhibitor (ISRIB); protein synthesis; vanishing white matter