title: The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct interfaces to eIF1, eIF2, eIF3, and eIF4G.
abstract: Eukaryotic translation initiation factor (eIF) 5 is crucial for the assembly of the eukaryotic preinitiation complex. This activity is mediated by the ability of its C-terminal HEAT domain to interact with eIF1, eIF2, and eIF3 in the multifactor complex and with eIF4G in the 48S complex. However, the binding sites for these factors on eIF5-C-terminal domain (CTD) have not been known. Here we present a homology model for eIF5-CTD based on the HEAT domain of eIF2Bepsilon. We show that the binding site for eIF2beta is located in a surface area containing aromatic and acidic residues (aromatic/acidic boxes), that the binding sites for eIF1 and eIF3c are located in a conserved surface region of basic residues, and that eIF4G binds eIF5-CTD at an interface overlapping with the acidic area. Mutations in these distinct eIF5 surface areas impair GCN4 translational control by disrupting preinitiation complex interactions. These results indicate that the eIF5 HEAT domain is a critical nucleation core for preinitiation complex assembly and function.
authors.affiliation: Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Chingakham Ranjit
authors.initials: CR
authors.lastname: Singh
authors.forename: Assen
authors.initials: A
authors.lastname: Marintchev
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Hall
authors.forename: Ernest M
authors.initials: EM
authors.lastname: Hannig
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Katsura
authors.initials: K
authors.lastname: Asano
mesh_terms: D001665:Binding Sites; D015977:Eukaryotic Initiation Factor-1 / Q000737:chemistry*; D015852:Eukaryotic Initiation Factor-2 / Q000737:chemistry*; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry*; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry*; D040061:Eukaryotic Initiation Factor-5 / Q000737:chemistry* / Q000502:physiology; D009154:Mutation; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D015977:Eukaryotic Initiation Factor-1; D015852:Eukaryotic Initiation Factor-2; D039621:Eukaryotic Initiation Factor-3; D039603:Eukaryotic Initiation Factor-4G; D040061:Eukaryotic Initiation Factor-5