3u7x: Difference between revisions
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[[ | ==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=''> | |||
== 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> | |||
</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> | |||
<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='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> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Eukaryotic initiation factor|Eukaryotic initiation factor]] | *[[Eukaryotic initiation factor|Eukaryotic initiation factor]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Arrowsmith, C H | [[Category: Arrowsmith, C H]] | ||
[[Category: Borden, K L.B | [[Category: Borden, K L.B]] | ||
[[Category: Bountra, C | [[Category: Bountra, C]] | ||
[[Category: Edwards, A M | [[Category: Edwards, A M]] | ||
[[Category: Nedyalkova, L | [[Category: Nedyalkova, L]] | ||
[[Category: Park, H | [[Category: Park, H]] | ||
[[Category: | [[Category: Structural genomic]] | ||
[[Category: Siddiqui, N | [[Category: Siddiqui, N]] | ||
[[Category: Tempel, W | [[Category: Tempel, W]] | ||
[[Category: Weigelt, J | [[Category: Weigelt, J]] | ||
[[Category: Wernimont, A K | [[Category: Wernimont, A K]] | ||
[[Category: Eif4e]] | [[Category: Eif4e]] | ||
[[Category: Mrna export]] | [[Category: Mrna export]] | ||
[[Category: Sgc]] | [[Category: Sgc]] | ||
[[Category: Translation]] | [[Category: Translation]] | ||
Revision as of 20:54, 9 December 2014
Crystal structure of the human eIF4E-4EBP1 peptide complex without capCrystal structure of the human eIF4E-4EBP1 peptide complex without cap
Structural highlights
Publication Abstract from PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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