Structure of eIF4E in complex with an eIF4G peptide supports a universal bipartite binding mode for protein translation

The association-dissociation of the cap-binding protein eIF4E with eIF4G is a key control step in eukaryotic translation. The paradigm on the eIF4E-eIF4G interaction states that eIF4G binds to the dorsal surface of eIF4E through a single canonical alpha-helical motif, while metazoan 4E-BPs (m4E-BPs) advantageously compete against eIF4G thanks to a bi-modal binding onto the canonical but additionally to a non-canonical motif in the lateral eIF4E surface thus inhibiting translation. Very recently, it has been shown that metazoan eIF4Gs share this extended binding interface with m4E-BPs, with significant implications on the understanding of translation regulation and the design of therapeutic molecules. Here we show the high-resolution structure of melon (Cucumis melo) eIF4E in complex with a melon eIF4G peptide, and propose the first eIF4E-eIF4G structural model for plants. Our structural data together with functional analyses demonstrate that plant eIF4G binds to eIF4E through both the canonical and non-canonical motifs, similarly to metazoan eIF4E-eIF4G complexes. As in the case of metazoan eIF4E-eIF4G, this may have very important practical implications, as plant eIF4E-eIF4G is also involved in a significant number of plant diseases. In the light of our results, a universal eukaryotic bipartite mode of binding to eIF4E is proposed.