6fc1

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Crystal structure of the eIF4E-Eap1p complex from Saccharomyces cerevisiae in the cap-bound state

Structural highlights

6fc1 is a 4 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:GOL, MGP
Gene:CDC33, TIF45, YOL139C (Baker's yeast), EAP1, YKL204W (Baker's yeast)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IF4E_YEAST] 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. [EAP1_YEAST] Can regulate translation through binding to eIF4E. Competes with eIF4G and p20 for binding to eIF4E in vivo and inhibits cap-dependent translation in vitro. Plays a role in cell growth and is implicated in the TOR signaling cascade. Functions independently of eIF4E to maintain genetic stability and to attenuate GCN4 translation upon TOR inactivation.[1] [2] [3]

Publication Abstract from PubMed

The interaction of the eukaryotic initiation factor 4G (eIF4G) with the cap-binding protein eIF4E initiates cap-dependent translation and is regulated by the 4E-binding proteins (4E-BPs), which compete with eIF4G to repress translation. Metazoan eIF4G and 4E-BPs interact with eIF4E via canonical and non-canonical motifs that bind to the dorsal and lateral surface of eIF4E in a bipartite recognition mode. However, previous studies pointed to mechanistic differences in how fungi and metazoans regulate protein synthesis. We present crystal structures of the yeast eIF4E bound to two yeast 4E-BPs, p20 and Eap1p, as well as crystal structures of a fungal eIF4E-eIF4G complex. We demonstrate that the core principles of molecular recognition of eIF4E are in fact highly conserved among translational activators and repressors in eukaryotes. Finally, we reveal that highly specialized structural motifs do exist and serve to modulate the affinity of protein-protein interactions that regulate cap-dependent translation initiation in fungi.

Structural motifs in eIF4G and 4E-BPs modulate their binding to eIF4E to regulate translation initiation in yeast.,Gruner S, Weber R, Peter D, Chung MY, Igreja C, Valkov E, Izaurralde E Nucleic Acids Res. 2018 Jul 27;46(13):6893-6908. doi: 10.1093/nar/gky542. PMID:30053226[4]

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

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Citations
4 reviews cite this structure
Control of the eIF4E activity: structural insights and pharmacological implications.
Romagnoli et al. (2021)
3 more
15 other articles
No citations found

References

  1. ↑ Cosentino GP, Schmelzle T, Haghighat A, Helliwell SB, Hall MN, Sonenberg N. Eap1p, a novel eukaryotic translation initiation factor 4E-associated protein in Saccharomyces cerevisiae. Mol Cell Biol. 2000 Jul;20(13):4604-13. PMID:10848587
  2. ↑ Chial HJ, Stemm-Wolf AJ, McBratney S, Winey M. Yeast Eap1p, an eIF4E-associated protein, has a separate function involving genetic stability. Curr Biol. 2000 Nov 30;10(23):1519-22. PMID:11114520
  3. ↑ Matsuo R, Kubota H, Obata T, Kito K, Ota K, Kitazono T, Ibayashi S, Sasaki T, Iida M, Ito T. The yeast eIF4E-associated protein Eap1p attenuates GCN4 translation upon TOR-inactivation. FEBS Lett. 2005 Apr 25;579(11):2433-8. doi: 10.1016/j.febslet.2005.03.043. PMID:15848184 doi:http://dx.doi.org/10.1016/j.febslet.2005.03.043
  4. ↑ Gruner S, Weber R, Peter D, Chung MY, Igreja C, Valkov E, Izaurralde E. Structural motifs in eIF4G and 4E-BPs modulate their binding to eIF4E to regulate translation initiation in yeast. Nucleic Acids Res. 2018 Jul 27;46(13):6893-6908. doi: 10.1093/nar/gky542. PMID:30053226 doi:http://dx.doi.org/10.1093/nar/gky542

Contents


6fc1, resolution 1.35Å

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