5T47

Crystal structure of the D. melanogaster eIF4E-eIF4G complex

Summary for 5T47

• Entry DOI: 10.2210/pdb5t47/pdb
• Descriptor: Eukaryotic translation initiation factor 4E, Eukaryotic translation initiation factor 4G, isoform A, GLYCEROL, ... (4 entities in total)
• Functional Keywords: translation, gene regulation, cap binding protein, 4e-binding protein, translation initiation, eif4f
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 4
• Total formula weight: 57503.04

Authors

Gruener, S.,Peter, D.,Weber, R.,Wohlbold, L.,Chung, M.-Y.,Weichenrieder, O.,Valkov, E.,Igreja, C.,Izaurralde, E. (deposition date: 2016-08-29, release date: 2016-10-26, Last modification date: 2024-01-17)

Primary citation

Gruner, S.,Peter, D.,Weber, R.,Wohlbold, L.,Chung, M.Y.,Weichenrieder, O.,Valkov, E.,Igreja, C.,Izaurralde, E.
The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation.
Mol.Cell, 64:467-479, 2016

PubMed Abstract: 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.

PubMed: 27773676
DOI: 10.1016/j.molcel.2016.09.020

Experimental method

X-RAY DIFFRACTION (2.2 Å)