1ej1

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COCRYSTAL STRUCTURE OF THE MESSENGER RNA 5' CAP-BINDING PROTEIN (EIF4E) BOUND TO 7-METHYL-GDP

Structural highlights

1ej1 is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:M7G
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[IF4E_MOUSE] 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. May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development (By similarity). Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The X-ray structure of the eukaryotic translation initiation factor 4E (eIF4E), bound to 7-methyl-GDP, has been determined at 2.2 A resolution. eIF4E recognizes 5' 7-methyl-G(5')ppp(5')N mRNA caps during the rate-limiting initiation step of translation. The protein resembles a cupped hand and consists of a curved, 8-stranded antiparallel beta sheet, backed by three long alpha helices. 7-methyl-GDP binds in a narrow cap-binding slot on the molecule's concave surface, where 7-methyl-guanine recognition is mediated by base sandwiching between two conserved tryptophans, plus formation of three hydrogen bonds and a van der Waals contact between its N7-methyl group and a third conserved tryptophan. The convex dorsal surface of the molecule displays a phylogenetically conserved hydrophobic/acidic portion, which may interact with other translation initiation factors and regulatory proteins.

Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP.,Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK Cell. 1997 Jun 13;89(6):951-61. PMID:9200613[2]

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

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Citations
97 reviews cite this structure
Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
Filipowicz et al. (2008)
96 more
308 other articles
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See Also

References

  1. ↑ Napoli I, Mercaldo V, Boyl PP, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, Mohr E, Massimi M, Falconi M, Witke W, Costa-Mattioli M, Sonenberg N, Achsel T, Bagni C. The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell. 2008 Sep 19;134(6):1042-54. doi: 10.1016/j.cell.2008.07.031. PMID:18805096 doi:http://dx.doi.org/10.1016/j.cell.2008.07.031
  2. ↑ Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK. Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell. 1997 Jun 13;89(6):951-61. PMID:9200613

Contents


1ej1, resolution 2.20Å

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