Crystal structure of the yeast eIF4A-eIF4G complex: An RNA-helicase controlled by protein-protein interactions

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 helicas...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-07, Vol.105 (28), p.9564-9569
Main Authors: Schütz, Patrick, Bumann, Mario, Oberholzer, Anselm Erich, Bieniossek, Christoph, Trachsel, Hans, Altmann, Michael, Baumann, Ulrich
Format: Article
Language:English
Subjects:
Adenosine triphosphatases
Amino acids
Binding Sites
Biological Sciences
Crystal structure
Crystals
Drug interactions
eukaryotic initiation factor 4A
eukaryotic initiation factor 4G
Eukaryotic Initiation Factor-4A - chemistry
Eukaryotic Initiation Factor-4A - metabolism
Eukaryotic Initiation Factor-4G - chemistry
Eukaryotic Initiation Factor-4G - metabolism
Messenger RNA
Molecular structure
Mutation
Peptide initiation factors
Phenotypes
Protein Binding
Protein Structure, Tertiary
protein-protein interactions
Proteins
RNA
RNA helicases
RNA Helicases - chemistry
RNA-protein interactions
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - metabolism
translation initiation factors
Yeast
Yeasts
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Summary: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-Å 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0800418105