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| ==Crystal structure of the human eIF4E-4EBP1 peptide complex without cap== | | ==Crystal structure of the human eIF4E-4EBP1 peptide complex without cap== |
| <StructureSection load='3u7x' size='340' side='right' caption='[[3u7x]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='3u7x' size='340' side='right'caption='[[3u7x]], [[Resolution|resolution]] 2.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3u7x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3smu 3smu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U7X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U7X FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3u7x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3smu 3smu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U7X FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF4E, EIF4EL1, EIF4F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></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=3u7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u7x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3u7x RCSB], [http://www.ebi.ac.uk/pdbsum/3u7x PDBsum]</span></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=3u7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u7x OCA], [https://pdbe.org/3u7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u7x RCSB], [https://www.ebi.ac.uk/pdbsum/3u7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u7x ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/IF4E_HUMAN IF4E_HUMAN]] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). 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. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.<ref>PMID:16271312</ref> [[http://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN]] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</ref> | | [https://www.uniprot.org/uniprot/IF4E_HUMAN IF4E_HUMAN] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). 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. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.<ref>PMID:16271312</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The eukaryotic translation initiation factor eIF4E plays key roles in cap-dependent translation and mRNA export. These functions rely on binding the 7-methylguanosine moiety (5'cap) to the 5'-end of all mRNAs. eIF4E is regulated by proteins such as eIF4G and eIF4E binding proteins (4EBPs) that bind the dorsal surface of eIF4E, distal to the cap binding site, and modulate cap binding activity. Both proteins increase the affinity of eIF4E for 5'cap. Our understanding of the allosteric effects and structural underpinnings of 4EBP1 or eIF4G binding can be advanced by structural data on cap-free eIF4E bound to one of these proteins. Here, we report the crystal structure of apo-eIF4E and cap-free eIF4E in complex with a 4EBP1 peptide. We also monitored 4EBP1 binding to cap-free eIF4E in solution using NMR. Together, these studies suggest that 4EBP1 transforms eIF4E into a cap-receptive state. NMR methods were also used to compare the allosteric routes activated by 4EBP1, eIF4G, and the arenavirus Z protein, a negative regulator of cap binding. We observed chemical shift perturbation at the dorsal binding site leading to alterations in the core of the protein, which were ultimately communicated to the unoccupied cap binding site of eIF4E. There were notable similarities between the routes taken by 4EBP1 and eIF4G and differences from the negative regulator Z. Thus, binding of 4EBP1 or eIF4G allosterically drives alterations throughout the protein that increase the affinity of eIF4E for the 5'cap.
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| Structural Insights into the Allosteric Effects of 4EBP1 on the Eukaryotic Translation Initiation Factor eIF4E.,Siddiqui N, Tempel W, Nedyalkova L, Volpon L, Wernimont AK, Osborne MJ, Park HW, Borden KL J Mol Biol. 2011 Dec 9. PMID:22178476<ref>PMID:22178476</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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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/> |
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| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Arrowsmith, C H]] | | [[Category: Large Structures]] |
| [[Category: Borden, K L.B]] | | [[Category: Arrowsmith CH]] |
| [[Category: Bountra, C]] | | [[Category: Borden KLB]] |
| [[Category: Edwards, A M]] | | [[Category: Bountra C]] |
| [[Category: Nedyalkova, L]] | | [[Category: Edwards AM]] |
| [[Category: Park, H]] | | [[Category: Nedyalkova L]] |
| [[Category: Structural genomic]]
| | [[Category: Park H]] |
| [[Category: Siddiqui, N]] | | [[Category: Siddiqui N]] |
| [[Category: Tempel, W]] | | [[Category: Tempel W]] |
| [[Category: Weigelt, J]] | | [[Category: Weigelt J]] |
| [[Category: Wernimont, A K]] | | [[Category: Wernimont AK]] |
| [[Category: Eif4e]]
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| [[Category: Mrna export]]
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| [[Category: Sgc]]
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| [[Category: Translation]]
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