4E-BPs require non-canonical 4E-binding motifs and a lateral surface of eIF4E to repress translation
| Autor: | Daniel Peter, Elisa Izaurralde, Cátia Igreja, Catrin Weiler |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Eukaryotic Initiation Factor-4E Amino Acid Motifs Molecular Sequence Data General Physics and Astronomy Plasma protein binding urologic and male genital diseases Bioinformatics Binding Competitive Article General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Eukaryotic translation Escherichia coli Protein biosynthesis Animals Drosophila Proteins Binding site Binding Sites Multidisciplinary biology EIF4G EIF4E General Chemistry biology.organism_classification Recombinant Proteins Cell biology Drosophila melanogaster Gene Expression Regulation chemistry Protein Biosynthesis Eukaryotic Initiation Factor-4G hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms5790 |
| Popis: | eIF4E-binding proteins (4E-BPs) are a widespread class of translational regulators that share a canonical (C) eIF4E-binding motif (4E-BM) with eIF4G. Consequently, 4E-BPs compete with eIF4G for binding to the dorsal surface on eIF4E to inhibit translation initiation. Some 4E-BPs contain non-canonical 4E-BMs (NC 4E-BMs), but the contribution of these motifs to the repressive mechanism—and whether these motifs are present in all 4E-BPs—remains unknown. Here, we show that the three annotated Drosophila melanogaster 4E-BPs contain NC 4E-BMs. These motifs bind to a lateral surface on eIF4E that is not used by eIF4G. This distinct molecular recognition mode is exploited by 4E-BPs to dock onto eIF4E–eIF4G complexes and effectively displace eIF4G from the dorsal surface of eIF4E. Our data reveal a hitherto unrecognized role for the NC4E-BMs and the lateral surface of eIF4E in 4E-BP-mediated translational repression, and suggest that bipartite 4E-BP mimics might represent efficient therapeutic tools to dampen translation during oncogenic transformation. eIF4E-binding proteins (4E-BPs) are a conserved class of translational repressors that play essential roles in the regulation of protein expression. Here, Igreja et al. indentify non-canonical interactions between 4E-BPs and eIF4E that are required to effectively displace eIF4G and inhibit translation. |
| Databáze: | OpenAIRE |
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