4ue8

Complex of D. melanogaster eIF4E with the 4E binding protein Thor

spinqualitylabelsall models 4ue8, resolution 1.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ue8 is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.1Å Ligands: NA, P4G Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IF4E_DROME 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. Publication Abstract from PubMed 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. Molecular Architecture of 4E-BP Translational Inhibitors Bound to eIF4E.,Peter D, Igreja C, Weber R, Wohlbold L, Weiler C, Ebertsch L, Weichenrieder O, Izaurralde E Mol Cell. 2015 Feb 18. pii: S1097-2765(15)00018-0. doi:, 10.1016/j.molcel.2015.01.017. PMID:25702871 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Eukaryotic initiation factor 3D structures

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