title: A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery.
abstract: The X-ray structure of the phylogenetically conserved middle portion of human eukaryotic initiation factor (eIF) 4GII has been determined at 2.4 A resolution, revealing a crescent-shaped domain consisting of ten alpha helices arranged as five HEAT repeats. Together with the ATP-dependent RNA helicase eIF4A, this HEAT domain suffices for 48S ribosomal complex formation with a picornaviral RNA internal ribosome entry site (IRES). Structure-based site-directed mutagenesis was used to identify two adjacent features on the surface of this essential component of the translation initiation machinery that, respectively, bind eIF4A and a picornaviral IRES. The structural and biochemical results provide mechanistic insights into both cap-dependent and cap-independent translation initiation.
authors.affiliation: Laboratories of Molecular Biophysics, The Rockefeller University, New York, NY 10021, USA.
authors.forename: J
authors.initials: J
authors.lastname: Marcotrigiano
authors.forename: I B
authors.initials: IB
authors.lastname: Lomakin
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
authors.forename: T V
authors.initials: TV
authors.lastname: Pestova
authors.forename: C U
authors.initials: CU
authors.lastname: Hellen
authors.forename: S K
authors.initials: SK
authors.lastname: Burley
mesh_terms: D001665:Binding Sites / Q000235:genetics; D018387:Codon, Initiator / Q000235:genetics; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D039603:Eukaryotic Initiation Factor-4G; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D010448:Peptide Initiation Factors / Q000737:chemistry* / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D018387:Codon, Initiator; D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors