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| | ==Solution structure of eIF4E3 in complex with m7GDP== | | ==Solution structure of eIF4E3 in complex with m7GDP== |
| - | <StructureSection load='4b6u' size='340' side='right' caption='[[4b6u]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='4b6u' size='340' side='right'caption='[[4b6u]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4b6u]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B6U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4b6u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B6U FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M7G:7N-METHYL-8-HYDROGUANOSINE-5-DIPHOSPHATE'>M7G</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4b6v|4b6v]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M7G:7N-METHYL-8-HYDROGUANOSINE-5-DIPHOSPHATE'>M7G</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=4b6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6u OCA], [http://pdbe.org/4b6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4b6u RCSB], [http://www.ebi.ac.uk/pdbsum/4b6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4b6u ProSAT]</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=4b6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6u OCA], [https://pdbe.org/4b6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b6u RCSB], [https://www.ebi.ac.uk/pdbsum/4b6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b6u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IF4E3_MOUSE IF4E3_MOUSE]] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis. May act as an inhibitor of EIF4E1 activity.<ref>PMID:15153109</ref> | + | [https://www.uniprot.org/uniprot/IF4E3_MOUSE IF4E3_MOUSE] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis. May act as an inhibitor of EIF4E1 activity.<ref>PMID:15153109</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4b6u" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4b6u" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Baguet, A]] | + | [[Category: Mus musculus]] |
| - | [[Category: Borden, K L.B]] | + | [[Category: Baguet A]] |
| - | [[Category: Culkjovic-Kraljcic, B]] | + | [[Category: Borden KLB]] |
| - | [[Category: Kornblatt, J A]] | + | [[Category: Culkjovic-Kraljcic B]] |
| - | [[Category: Osborne, M J]] | + | [[Category: Kornblatt JA]] |
| - | [[Category: Volpon, L]] | + | [[Category: Osborne MJ]] |
| - | [[Category: Translation]]
| + | [[Category: Volpon L]] |
| Structural highlights
Function
IF4E3_MOUSE Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis. May act as an inhibitor of EIF4E1 activity.[1]
Publication Abstract from PubMed
Recognition of the methyl-7-guanosine (mG) cap structure on mRNA is an essential feature of mRNA metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, mRNA export, proliferation, and oncogenic transformation dependent on this cap-binding activity. eIF4E-cap recognition is mediated via complementary charge interactions of the positively charged mG cap between the negative pi-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily, eIF4E3, specifically binds the mG cap in the absence of an aromatic sandwich, using instead a different spatial arrangement of residues to provide the necessary electrostatic and van der Waals contacts. Contacts are much more extensive between eIF4E3-cap than other family members. Structural analyses of other cap-binding proteins indicate this recognition mode is atypical. We demonstrate that eIF4E3 relies on this cap-binding activity to act as a tumor suppressor, competing with the growth-promoting functions of eIF4E. In fact, reduced eIF4E3 in high eIF4E cancers suggests that eIF4E3 underlies a clinically relevant inhibitory mechanism that is lost in some malignancies. Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant.
eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition.,Osborne MJ, Volpon L, Kornblatt JA, Culjkovic-Kraljacic B, Baguet A, Borden KL Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3877-82. doi:, 10.1073/pnas.1216862110. Epub 2013 Feb 19. PMID:23431134[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Joshi B, Cameron A, Jagus R. Characterization of mammalian eIF4E-family members. Eur J Biochem. 2004 Jun;271(11):2189-203. PMID:15153109 doi:http://dx.doi.org/10.1111/j.1432-1033.2004.04149.x
- ↑ Osborne MJ, Volpon L, Kornblatt JA, Culjkovic-Kraljacic B, Baguet A, Borden KL. eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3877-82. doi:, 10.1073/pnas.1216862110. Epub 2013 Feb 19. PMID:23431134 doi:http://dx.doi.org/10.1073/pnas.1216862110
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