title: Crystal structure of the yeast eIF4A-eIF4G complex: an RNA-helicase controlled by protein-protein interactions.
abstract: Translation initiation factors eIF4A and eIF4G form, together with the cap-binding factor eIF4E, the eIF4F complex, which is crucial for recruiting the small ribosomal subunit to the mRNA 5' end and for subsequent scanning and searching for the start codon. eIF4A is an ATP-dependent RNA helicase whose activity is stimulated by binding to eIF4G. We report here the structure of the complex formed by yeast eIF4G's middle domain and full-length eIF4A at 2.6-A resolution. eIF4A shows an extended conformation where eIF4G holds its crucial DEAD-box sequence motifs in a productive conformation, thus explaining the stimulation of eIF4A's activity. A hitherto undescribed interaction involves the amino acid Trp-579 of eIF4G. Mutation to alanine results in decreased binding to eIF4A and a temperature-sensitive phenotype of yeast cells that carry a Trp579Ala mutation as its sole source for eIF4G. Conformational changes between eIF4A's closed and open state provide a model for its RNA-helicase activity.
authors.affiliation: Departement für Chemie und Biochemie, Universität Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schütz
authors.forename: Mario
authors.initials: M
authors.lastname: Bumann
authors.forename: Anselm Erich
authors.initials: AE
authors.lastname: Oberholzer
authors.forename: Christoph
authors.initials: C
authors.lastname: Bieniossek
authors.forename: Hans
authors.initials: H
authors.lastname: Trachsel
authors.forename: Michael
authors.initials: M
authors.lastname: Altmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
mesh_terms: D001665:Binding Sites; D039601:Eukaryotic Initiation Factor-4A / Q000737:chemistry* / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D039603:Eukaryotic Initiation Factor-4G; D029701:Saccharomyces cerevisiae Proteins; D039601:Eukaryotic Initiation Factor-4A; D020365:RNA Helicases