4UED: Complex of human eIF4E with the 4E binding protein 4E-BP1

Citation:
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.
PDB ID: 4UEDDownload
MMDB ID: 127306
PDB Deposition Date: 2014/12/16
Updated in MMDB: 2018/07
Experimental Method:
x-ray diffraction
Resolution: 1.75  Å
Source Organism:
Similar Structures:
Biological Unit for 4UED: dimeric; determined by author and by software (PISA)
Molecular Components in 4UED
Label Count Molecule
Proteins (2 molecules)
1
Eukaryotic Translation Initiation Factor 4E(Gene symbol: EIF4E)
Molecule annotation
1
Eukaryotic Translation Factor 4e-binding Protein 1(Gene symbol: EIF4EBP1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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