5t47

Crystal structure of the D. melanogaster eIF4E-eIF4G complexCrystal structure of the D. melanogaster eIF4E-eIF4G complex

Structural highlights

5t47 is a 4 chain structure with sequence from Drome. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	eIF-4E, Eif4e, EIF4F, CG4035 (DROME), eIF4G, eIF-4G, eIF4G-RA, CG10811, Dmel_CG10811 (DROME)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IF4E_DROME] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures.^[1]

Publication Abstract from PubMed

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.

The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation.,Gruner S, Peter D, Weber R, Wohlbold L, Chung MY, Weichenrieder O, Valkov E, Igreja C, Izaurralde E Mol Cell. 2016 Oct 19. pii: S1097-2765(16)30569-X. doi:, 10.1016/j.molcel.2016.09.020. PMID:27773676^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lavoie CA, Lachance PE, Sonenberg N, Lasko P. Alternatively spliced transcripts from the Drosophila eIF4E gene produce two different Cap-binding proteins. J Biol Chem. 1996 Jul 5;271(27):16393-8. PMID:8663200
↑ Gruner S, Peter D, Weber R, Wohlbold L, Chung MY, Weichenrieder O, Valkov E, Igreja C, Izaurralde E. The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation. Mol Cell. 2016 Oct 19. pii: S1097-2765(16)30569-X. doi:, 10.1016/j.molcel.2016.09.020. PMID:27773676 doi:http://dx.doi.org/10.1016/j.molcel.2016.09.020

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OCA

[1] Lavoie CA, Lachance PE, Sonenberg N, Lasko P. Alternatively spliced transcripts from the Drosophila eIF4E gene produce two different Cap-binding proteins. J Biol Chem. 1996 Jul 5;271(27):16393-8. PMID:8663200

[2] Gruner S, Peter D, Weber R, Wohlbold L, Chung MY, Weichenrieder O, Valkov E, Igreja C, Izaurralde E. The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation. Mol Cell. 2016 Oct 19. pii: S1097-2765(16)30569-X. doi:, 10.1016/j.molcel.2016.09.020. PMID:27773676 doi:http://dx.doi.org/10.1016/j.molcel.2016.09.020

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