6fc3

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Crystal structure of the eIF4E-p20 complex from Saccharomyces cerevisiae

Structural highlights

6fc3 is a 2 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, ZN
Gene:CDC33, TIF45, YOL139C (Baker's yeast), CAF20, CAF2, CAP20, YOR276W, O5453W (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. [CAF20_YEAST] Acts as an inhibitor of cap-dependent translation. Competes with eIF4G1/TIF4631 and EAP1 for binding to eIF4E/TIF45 and interferes with the formation of the eIF4F complex, inhibiting translation and stabilizing mRNA. Binding affinity for eIF4E/TIF45 is 10-fold less than that of eIF4G1/TIF4631. Required for induction of pseudohyphal growth in response to nitrogen limitation, probably by regulating STE12 translation.[1] [2] [3] [4] [5] [6] [7]

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[8]

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

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Citations
3 reviews cite this structure
Biochemical and Structural Insights into the Eukaryotic Translation Initiation Factor eIF4E.
Volpon et al. (2019)
2 more
14 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. ↑ Ramirez CV, Vilela C, Berthelot K, McCarthy JE. Modulation of eukaryotic mRNA stability via the cap-binding translation complex eIF4F. J Mol Biol. 2002 May 10;318(4):951-62. PMID:12054793 doi:http://dx.doi.org/10.1016/S0022-2836(02)00162-6
  3. ↑ von der Haar T, McCarthy JE. Intracellular translation initiation factor levels in Saccharomyces cerevisiae and their role in cap-complex function. Mol Microbiol. 2002 Oct;46(2):531-44. PMID:12406227
  4. ↑ Park YU, Hur H, Ka M, Kim J. Identification of translational regulation target genes during filamentous growth in Saccharomyces cerevisiae: regulatory role of Caf20 and Dhh1. Eukaryot Cell. 2006 Dec;5(12):2120-7. Epub 2006 Oct 13. PMID:17041186 doi:http://dx.doi.org/EC.00121-06
  5. ↑ Ibrahimo S, Holmes LE, Ashe MP. Regulation of translation initiation by the yeast eIF4E binding proteins is required for the pseudohyphal response. Yeast. 2006 Oct-Nov;23(14-15):1075-88. PMID:17083129 doi:http://dx.doi.org/10.1002/yea.1415
  6. ↑ Altmann M, Schmitz N, Berset C, Trachsel H. A novel inhibitor of cap-dependent translation initiation in yeast: p20 competes with eIF4G for binding to eIF4E. EMBO J. 1997 Mar 3;16(5):1114-21. doi: 10.1093/emboj/16.5.1114. PMID:9118949 doi:http://dx.doi.org/10.1093/emboj/16.5.1114
  7. ↑ Ptushkina M, von der Haar T, Vasilescu S, Frank R, Birkenhager R, McCarthy JE. Cooperative modulation by eIF4G of eIF4E-binding to the mRNA 5' cap in yeast involves a site partially shared by p20. EMBO J. 1998 Aug 17;17(16):4798-808. PMID:9707439 doi:http://dx.doi.org/10.1093/emboj/17.16.4798
  8. ↑ 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


6fc3, resolution 1.75Å

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