title: Clues to the mechanism of action of eIF2B, the guanine-nucleotide-exchange factor for translation initiation.
abstract: A variety of cellular processes rely on G-proteins, which cycle through active GTP-bound and inactive GDP-bound forms. The switch between these states is commonly regulated by GEFs (guanine-nucleotide-exchange factors) and GAPs (GTPase-activating proteins). Although G-proteins have structural similarity, GEFs are very diverse proteins. A complex example of this system is seen in eukaryotic translation initiation between eIF (eukaryotic initiation factor) 2, a G-protein, its five-subunit GEF, eIF2B, and its GAP, eIF5. eIF2 delivers Met-tRNA(i) (initiator methionyl-tRNA) to the 40S ribosomal subunit before mRNA binding. Upon AUG recognition, eIF2 hydrolyses GTP, aided by eIF5. eIF2B then re-activates eIF2 by removing GDP, thereby promoting association of GTP. In the present article, we review data from studies of representative G-protein-GEF pairs and compare these with observations from our research on eIF2 and eIF2B to propose a model for how interactions between eIF2B and eIF2 promote guanine nucleotide exchange.
authors.affiliation: Faculty of Life Sciences, The Michael Smith Building, The University of Manchester, Oxford Road, Manchester, UK.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Mohammad-Qureshi
authors.forename: Martin D
authors.initials: MD
authors.lastname: Jennings
authors.forename: Graham D
authors.initials: GD
authors.lastname: Pavitt
mesh_terms: D002384:Catalysis; D020717:Eukaryotic Initiation Factor-2B / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D010442:Peptide Chain Initiation, Translational; D011485:Protein Binding
chemical_list: D020717:Eukaryotic Initiation Factor-2B; D008024:Ligands