5ABX

Complex of C. elegans eIF4E-3 with the 4E-binding protein Mextli and cap analog

Summary for 5ABX

• Entry DOI: 10.2210/pdb5abx/pdb
• Related: 5ABU 5ABV 5ABY
• Descriptor: EUKARYOTIC TRANSLATION INITIATION FACTOR 4E-3, 4E-BINDING PROTEIN MEXTLI, 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: translation, gene regulation, cap binding protein, 4e binding protein
• Biological source: CAENORHABDITIS ELEGANS (ROUNDWORM); More
• Total number of polymer chains: 2
• Total formula weight: 27953.30

Authors

Peter, D.,Weichenrieder, O. (deposition date: 2015-08-09, release date: 2015-09-02, Last modification date: 2024-05-08)

Primary citation

Peter, D.,Weber, R.,Koene, C.,Chung, M.-Y.,Ebertsch, L.,Truffault, V.,Weichenrieder, O.,Igreja, C.,Izaurralde, E.
Mextli Proteins Use Both Canonical Bipartite and Novel Tripartite Binding Modes to Form Eif4E Complexes that Display Differential Sensitivity to 4E-BP Regulation
Genes Dev., 29:1835-, 2015

PubMed Abstract: The eIF4E-binding proteins (4E-BPs) are a diverse class of translation regulators that share a canonical eIF4E-binding motif (4E-BM) with eIF4G. Consequently, they compete with eIF4G for binding to eIF4E, thereby inhibiting translation initiation. Mextli (Mxt) is an unusual 4E-BP that promotes translation by also interacting with eIF3. Here we present the crystal structures of the eIF4E-binding regions of the Drosophila melanogaster (Dm) and Caenorhabditis elegans (Ce) Mxt proteins in complex with eIF4E in the cap-bound and cap-free states. The structures reveal unexpected evolutionary plasticity in the eIF4E-binding mode, with a classical bipartite interface for Ce Mxt and a novel tripartite interface for Dm Mxt. Both interfaces comprise a canonical helix and a noncanonical helix that engage the dorsal and lateral surfaces of eIF4E, respectively. Remarkably, Dm Mxt contains a C-terminal auxiliary helix that lies anti-parallel to the canonical helix on the eIF4E dorsal surface. In contrast to the eIF4G and Ce Mxt complexes, the Dm eIF4E-Mxt complexes are resistant to competition by bipartite 4E-BPs, suggesting that Dm Mxt can bind eIF4E when eIF4G binding is inhibited. Our results uncovered unexpected diversity in the binding modes of 4E-BPs, resulting in eIF4E complexes that display differential sensitivity to 4E-BP regulation.

PubMed: 26294658
DOI: 10.1101/GAD.269068.115

Experimental method

X-RAY DIFFRACTION (1.66 Å)