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| | <StructureSection load='4uea' size='340' side='right'caption='[[4uea]], [[Resolution|resolution]] 2.62Å' scene=''> | | <StructureSection load='4uea' size='340' side='right'caption='[[4uea]], [[Resolution|resolution]] 2.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uea]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UEA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uea]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UEA FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ue8|4ue8]], [[4ue9|4ue9]], [[4ueb|4ueb]], [[4uec|4uec]], [[4ued|4ued]]</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4uea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uea OCA], [https://pdbe.org/4uea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uea RCSB], [https://www.ebi.ac.uk/pdbsum/4uea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uea ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uea OCA], [http://pdbe.org/4uea PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uea RCSB], [http://www.ebi.ac.uk/pdbsum/4uea PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uea ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IF4E_DROME 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.<ref>PMID:8663200</ref> | + | [https://www.uniprot.org/uniprot/IF4E_DROME 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.<ref>PMID:8663200</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Eukaryotic initiation factor|Eukaryotic initiation factor]] | + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Peter, D]] | + | [[Category: Peter D]] |
| - | [[Category: Weichenrieder, O]] | + | [[Category: Weichenrieder O]] |
| - | [[Category: 4e binding protein]]
| + | |
| - | [[Category: Cap binding protein]]
| + | |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Translation]]
| + | |
| - | [[Category: Translational repression]]
| + | |
| Structural highlights
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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lavoie CA, Lachance PE, Sonenberg N, Lasko P. Alternatively spliced transcripts from the Drosophila eIF4E gene produce two different Cap-binding proteins. J Biol Chem. 1996 Jul 5;271(27):16393-8. PMID:8663200
- ↑ 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. 2015 Feb 18. pii: S1097-2765(15)00018-0. doi:, 10.1016/j.molcel.2015.01.017. PMID:25702871 doi:http://dx.doi.org/10.1016/j.molcel.2015.01.017
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