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| - | ==THE CRYSTAL STRUCTURE OF THE EXON JUNCTION COMPLEX AT 2.2 A RESOLUTION== | + | |
| - | <StructureSection load='2j0s' size='340' side='right' caption='[[2j0s]], [[Resolution|resolution]] 2.21Å' scene=''> | + | ==The crystal structure of the Exon Junction Complex at 2.2 A resolution== |
| | + | <StructureSection load='2j0s' size='340' side='right'caption='[[2j0s]], [[Resolution|resolution]] 2.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2j0s]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J0S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J0S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2j0s]] is a 5 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=2J0S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J0S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.21Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1p27|1p27]], [[2j0q|2j0q]], [[2j0u|2j0u]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2j0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j0s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j0s RCSB], [http://www.ebi.ac.uk/pdbsum/2j0s 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=2j0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j0s OCA], [https://pdbe.org/2j0s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j0s RCSB], [https://www.ebi.ac.uk/pdbsum/2j0s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j0s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RBM8A_HUMAN RBM8A_HUMAN]] Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The heterodimer MAGOH-RBM8A interacts with PYM that function to enhance the translation of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Remains associated with mRNAs in the cytoplasm until the mRNAs engage the translation machinery. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Complex with MAGOH is a component of the nonsense mediated decay (NMD) pathway.<ref>PMID:12121612</ref> <ref>PMID:12718880</ref> <ref>PMID:12730685</ref> <ref>PMID:16209946</ref> <ref>PMID:19409878</ref> [[http://www.uniprot.org/uniprot/MGN_HUMAN MGN_HUMAN]] Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Remains associated with the mRNA after its export to the cytoplasm and require translation of the mRNA for removal. The heterodimer MAGOH-RBM8A interacts with PYM that function to enhance the translation of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex.<ref>PMID:12730685</ref> <ref>PMID:16209946</ref> [[http://www.uniprot.org/uniprot/CASC3_HUMAN CASC3_HUMAN]] Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons (By similarity). May play a role in mRNA transport (By similarity). Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homopolymer.<ref>PMID:17652158</ref> <ref>PMID:17375189</ref> | + | [https://www.uniprot.org/uniprot/RBM8A_HUMAN RBM8A_HUMAN] Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The heterodimer MAGOH-RBM8A interacts with PYM that function to enhance the translation of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Remains associated with mRNAs in the cytoplasm until the mRNAs engage the translation machinery. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Complex with MAGOH is a component of the nonsense mediated decay (NMD) pathway.<ref>PMID:12121612</ref> <ref>PMID:12718880</ref> <ref>PMID:12730685</ref> <ref>PMID:16209946</ref> <ref>PMID:19409878</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j0/2j0s_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j0/2j0s_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2j0s ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2j0s" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Helicase|Helicase]] | + | *[[Helicase 3D structures|Helicase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Bono, F]] | + | [[Category: Large Structures]] |
| - | [[Category: Conti, E]] | + | [[Category: Bono F]] |
| - | [[Category: Ebert, J]] | + | [[Category: Conti E]] |
| - | [[Category: Lorentzen, E]] | + | [[Category: Ebert J]] |
| - | [[Category: Atp-binding]]
| + | [[Category: Lorentzen E]] |
| - | [[Category: Dead-box helicase]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Ejc]]
| + | |
| - | [[Category: Helicase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mrna processing]]
| + | |
| - | [[Category: Mrna splicing]]
| + | |
| - | [[Category: Mrna transport]]
| + | |
| - | [[Category: Nonsense-mediated mrna decay]]
| + | |
| - | [[Category: Nuclear protein]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Rna-binding]]
| + | |
| - | [[Category: Rrna processing]]
| + | |
| - | [[Category: Transport]]
| + | |
| Structural highlights
Function
RBM8A_HUMAN Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The heterodimer MAGOH-RBM8A interacts with PYM that function to enhance the translation of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Remains associated with mRNAs in the cytoplasm until the mRNAs engage the translation machinery. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Complex with MAGOH is a component of the nonsense mediated decay (NMD) pathway.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The exon junction complex (EJC) plays a major role in posttranscriptional regulation of mRNA in metazoa. The EJC is deposited onto mRNA during splicing and is transported to the cytoplasm where it influences translation, surveillance, and localization of the spliced mRNA. The complex is formed by the association of four proteins (eIF4AIII, Barentsz [Btz], Mago, and Y14), mRNA, and ATP. The 2.2 A resolution structure of the EJC reveals how it stably locks onto mRNA. The DEAD-box protein eIF4AIII encloses an ATP molecule and provides the binding sites for six ribonucleotides. Btz wraps around eIF4AIII and stacks against the 5' nucleotide. An intertwined network of interactions anchors Mago-Y14 and Btz at the interface between the two domains of eIF4AIII, effectively stabilizing the ATP bound state. Comparison with the structure of the eIF4AIII-Btz subcomplex that we have also determined reveals that large conformational changes are required upon EJC assembly and disassembly.
The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA.,Bono F, Ebert J, Lorentzen E, Conti E Cell. 2006 Aug 25;126(4):713-25. PMID:16923391[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dostie J, Dreyfuss G. Translation is required to remove Y14 from mRNAs in the cytoplasm. Curr Biol. 2002 Jul 9;12(13):1060-7. PMID:12121612
- ↑ Gehring NH, Neu-Yilik G, Schell T, Hentze MW, Kulozik AE. Y14 and hUpf3b form an NMD-activating complex. Mol Cell. 2003 Apr;11(4):939-49. PMID:12718880
- ↑ Fribourg S, Gatfield D, Izaurralde E, Conti E. A novel mode of RBD-protein recognition in the Y14-Mago complex. Nat Struct Biol. 2003 Jun;10(6):433-9. PMID:12730685 doi:10.1038/nsb926
- ↑ Gehring NH, Kunz JB, Neu-Yilik G, Breit S, Viegas MH, Hentze MW, Kulozik AE. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005 Oct 7;20(1):65-75. PMID:16209946 doi:http://dx.doi.org/S1097-2765(05)01554-6
- ↑ Lee HC, Choe J, Chi SG, Kim YK. Exon junction complex enhances translation of spliced mRNAs at multiple steps. Biochem Biophys Res Commun. 2009 Jul 3;384(3):334-40. doi:, 10.1016/j.bbrc.2009.04.123. Epub 2009 May 3. PMID:19409878 doi:http://dx.doi.org/10.1016/j.bbrc.2009.04.123
- ↑ Bono F, Ebert J, Lorentzen E, Conti E. The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA. Cell. 2006 Aug 25;126(4):713-25. PMID:16923391 doi:10.1016/j.cell.2006.08.006
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