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| | <StructureSection load='5xln' size='340' side='right'caption='[[5xln]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='5xln' size='340' side='right'caption='[[5xln]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xln]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XLN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XLN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xln]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XLN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XLN FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF4E2, EIF4EL3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TARS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.9Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Threonine--tRNA_ligase Threonine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.3 6.1.1.3] </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=5xln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xln OCA], [https://pdbe.org/5xln PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xln RCSB], [https://www.ebi.ac.uk/pdbsum/5xln PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xln 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=5xln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xln OCA], [http://pdbe.org/5xln PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xln RCSB], [http://www.ebi.ac.uk/pdbsum/5xln PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xln ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IF4E2_HUMAN IF4E2_HUMAN]] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation (PubMed:9582349, PubMed:17368478, PubMed:25624349). Acts as a repressor of translation initiation (PubMed:22751931). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (By similarity).[UniProtKB:Q8BMB3]<ref>PMID:17368478</ref> <ref>PMID:22751931</ref> <ref>PMID:25624349</ref> <ref>PMID:9582349</ref> | + | [https://www.uniprot.org/uniprot/IF4E2_HUMAN IF4E2_HUMAN] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation (PubMed:9582349, PubMed:17368478, PubMed:25624349). Acts as a repressor of translation initiation (PubMed:22751931). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (By similarity).[UniProtKB:Q8BMB3]<ref>PMID:17368478</ref> <ref>PMID:22751931</ref> <ref>PMID:25624349</ref> <ref>PMID:9582349</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | A fundamental question in biology is how vertebrates evolved and differ from invertebrates, and little is known about differences in the regulation of translation in the two systems. Herein, we identify a threonyl-tRNA synthetase (TRS)-mediated translation initiation machinery that specifically interacts with eIF4E homologous protein, and forms machinery that is structurally analogous to the eIF4F-mediated translation initiation machinery via the recruitment of other translation initiation components. Biochemical and RNA immunoprecipitation analyses coupled to sequencing suggest that this machinery emerged as a gain-of-function event in the vertebrate lineage, and it positively regulates the translation of mRNAs required for vertebrate development. Collectively, our findings demonstrate that TRS evolved to regulate vertebrate translation initiation via its dual role as a scaffold for the assembly of initiation components and as a selector of target mRNAs. This work highlights the functional significance of aminoacyl-tRNA synthetases in the emergence and control of higher order organisms.
| + | |
| | | | |
| - | A threonyl-tRNA synthetase-mediated translation initiation machinery.,Jeong SJ, Park S, Nguyen LT, Hwang J, Lee EY, Giong HK, Lee JS, Yoon I, Lee JH, Kim JH, Kim HK, Kim D, Yang WS, Kim SY, Lee CY, Yu K, Sonenberg N, Kim MH, Kim S Nat Commun. 2019 Mar 22;10(1):1357. doi: 10.1038/s41467-019-09086-0. PMID:30902983<ref>PMID:30902983</ref>
| + | ==See Also== |
| - | | + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5xln" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Threonine--tRNA ligase]]
| + | [[Category: Hwang J]] |
| - | [[Category: Hwang, J]] | + | [[Category: Kim MH]] |
| - | [[Category: Kim, M H]] | + | [[Category: Nguyen LT]] |
| - | [[Category: Nguyen, L T]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Rna binding protein-ligase complex]]
| + | |
| - | [[Category: Tr]]
| + | |
| Structural highlights
Function
IF4E2_HUMAN Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation (PubMed:9582349, PubMed:17368478, PubMed:25624349). Acts as a repressor of translation initiation (PubMed:22751931). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (By similarity).[UniProtKB:Q8BMB3][1] [2] [3] [4]
See Also
References
- ↑ Rosettani P, Knapp S, Vismara MG, Rusconi L, Cameron AD. Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms. J Mol Biol. 2007 May 4;368(3):691-705. Epub 2007 Feb 20. PMID:17368478 doi:10.1016/j.jmb.2007.02.019
- ↑ Morita M, Ler LW, Fabian MR, Siddiqui N, Mullin M, Henderson VC, Alain T, Fonseca BD, Karashchuk G, Bennett CF, Kabuta T, Higashi S, Larsson O, Topisirovic I, Smith RJ, Gingras AC, Sonenberg N. A novel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development. Mol Cell Biol. 2012 Sep;32(17):3585-93. doi: 10.1128/MCB.00455-12. Epub 2012 Jul , 2. PMID:22751931 doi:http://dx.doi.org/10.1128/MCB.00455-12
- ↑ von Stechow L, Typas D, Carreras Puigvert J, Oort L, Siddappa R, Pines A, Vrieling H, van de Water B, Mullenders LH, Danen EH. The E3 ubiquitin ligase ARIH1 protects against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. Mol Cell Biol. 2015 Apr;35(7):1254-68. doi: 10.1128/MCB.01152-14. Epub 2015 Jan, 26. PMID:25624349 doi:http://dx.doi.org/10.1128/MCB.01152-14
- ↑ Rom E, Kim HC, Gingras AC, Marcotrigiano J, Favre D, Olsen H, Burley SK, Sonenberg N. Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein. J Biol Chem. 1998 May 22;273(21):13104-9. PMID:9582349
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