Structural highlights
5t48 is a 2 chain structure with sequence from Drome. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| 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.
See Also
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
