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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 2 - Biochemistry (E. Izaurralde)     Display Documents



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ID: 732872.0, MPI für Entwicklungsbiologie / Abteilung 2 - Biochemistry (E. Izaurralde)
The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation
Authors:Gruner, S.; Peter, D.; Weber, R.; Wohlbold, L.; Chung, M. Y.; Weichenrieder, O.; Valkov, E.; Igreja, C.; Izaurralde, E.
Date of Publication (YYYY-MM-DD):2016-11-03
Title of Journal:Mol Cell
Volume:64
Issue / Number:3
Start Page:467
End Page:479
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Eukaryotic initiation factor 4G (eIF4G) plays a central role in translation initiation through its interactions with the cap-binding protein eIF4E. This interaction is a major drug target for repressing translation and is naturally regulated by 4E-binding proteins (4E-BPs). 4E-BPs and eIF4G compete for binding to the eIF4E dorsal surface via a shared canonical 4E-binding motif, but also contain auxiliary eIF4E-binding sequences, which were assumed to contact non-overlapping eIF4E surfaces. However, it is unknown how metazoan eIF4G auxiliary sequences bind eIF4E. Here, we describe crystal structures of human and Drosophila melanogaster eIF4E-eIF4G complexes, which unexpectedly reveal that the eIF4G auxiliary sequences bind to the lateral surface of eIF4E, using a similar mode to that of 4E-BPs. Our studies provide a molecular model of the eIF4E-eIF4G complex, shed light on the competition mechanism of 4E-BPs, and enable the rational design of selective eIF4G inhibitors to dampen dysregulated translation in disease.
Free Keywords:4e-bp; eIF4F; protein-protein interaction; translation initiation; translational inhibitors; translational regulation
External Publication Status:published
Document Type:Article
Communicated by:root
Affiliations:MPI für Entwicklungsbiologie/Abteilung 2 - Biochemie (Elisa Izaurralde)
External Affiliations:Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tubingen, Germany. Electronic address: oliver.weichenrieder@tuebingen.mpg.de. Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tubingen, Germany. Electronic address: elisa.izaurralde@tuebingen.mpg.de.
Identifiers:ISSN:1097-4164 (Electronic) 1097-2765 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/27773676 [ID No:2]
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