4UEA
Complex of D. melanogaster eIF4E with a designed 4E-binding protein (Form I)
Summary for 4UEA
| Entry DOI | 10.2210/pdb4uea/pdb |
| Related | 4UE8 4UE9 4UEB 4UEC 4UED |
| Descriptor | EUKARYOTIC TRANSLATION INITIATION FACTOR 4E, DESIGNED 4E-BP (2 entities in total) |
| Functional Keywords | translation, gene regulation, cap binding protein, 4e binding protein, translational repression |
| Biological source | DROSOPHILA MELANOGASTER (FRUIT FLY) More |
| Total number of polymer chains | 6 |
| Total formula weight | 79058.89 |
| Authors | Peter, D.,Weichenrieder, O. (deposition date: 2014-12-16, release date: 2015-02-25, Last modification date: 2023-12-20) |
| Primary citation | Peter, D.,Igreja, C.,Weber, R.,Wohlbold, L.,Weiler, C.,Ebertsch, L.,Weichenrieder, O.,Izaurralde, E. Molecular Architecture of 4E-BP Translational Inhibitors Bound to Eif4E. Mol.Cell, 57:1074-, 2015 Cited by PubMed Abstract: The eIF4E-binding proteins (4E-BPs) represent a diverse class of translation inhibitors that are often deregulated in cancer cells. 4E-BPs inhibit translation by competing with eIF4G for binding to eIF4E through an interface that consists of canonical and non-canonical eIF4E-binding motifs connected by a linker. The lack of high-resolution structures including the linkers, which contain phosphorylation sites, limits our understanding of how phosphorylation inhibits complex formation. Furthermore, the binding mechanism of the non-canonical motifs is poorly understood. Here, we present structures of human eIF4E bound to 4E-BP1 and fly eIF4E bound to Thor, 4E-T, and eIF4G. These structures reveal architectural elements that are unique to 4E-BPs and provide insight into the consequences of phosphorylation. Guided by these structures, we designed and crystallized a 4E-BP mimic that shows increased repressive activity. Our studies pave the way for the rational design of 4E-BP mimics as therapeutic tools to decrease translation during oncogenic transformation. PubMed: 25702871DOI: 10.1016/J.MOLCEL.2015.01.017 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.62 Å) |
Structure validation
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