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| | ==Crystal structure of the N-terminal domain of human UAP56== | | ==Crystal structure of the N-terminal domain of human UAP56== |
| - | <StructureSection load='1t6n' size='340' side='right' caption='[[1t6n]], [[Resolution|resolution]] 1.94Å' scene=''> | + | <StructureSection load='1t6n' size='340' side='right'caption='[[1t6n]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1t6n]] 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=1T6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T6N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1t6n]] 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=1T6N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T6N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</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]] 1.94Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1t5i|1t5i]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1t6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t6n OCA], [https://pdbe.org/1t6n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t6n RCSB], [https://www.ebi.ac.uk/pdbsum/1t6n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t6n 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=1t6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t6n OCA], [http://pdbe.org/1t6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t6n RCSB], [http://www.ebi.ac.uk/pdbsum/1t6n PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DX39B_HUMAN DX39B_HUMAN]] Component of the THO subcomplex of the TREX complex. The TREX complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is recruited to spliced mRNAs by a transcription-independent mechanism. Binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export. The recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. DDX39B functions as a bridge between ALYREF/THOC4 and the THO complex. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. The recruitment of the TREX complex to the intronless viral mRNA occurs via an interaction between KSHV ORF57 protein and ALYREF/THOC4.<ref>PMID:9242493</ref> <ref>PMID:11675789</ref> <ref>PMID:15833825</ref> <ref>PMID:15998806</ref> <ref>PMID:17190602</ref> <ref>PMID:17562711</ref> <ref>PMID:18974867</ref> <ref>PMID:15585580</ref> Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2 and ALYREF/THOC4.<ref>PMID:9242493</ref> <ref>PMID:11675789</ref> <ref>PMID:15833825</ref> <ref>PMID:15998806</ref> <ref>PMID:17190602</ref> <ref>PMID:17562711</ref> <ref>PMID:18974867</ref> <ref>PMID:15585580</ref> | + | [https://www.uniprot.org/uniprot/DX39B_HUMAN DX39B_HUMAN] Component of the THO subcomplex of the TREX complex. The TREX complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is recruited to spliced mRNAs by a transcription-independent mechanism. Binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export. The recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. DDX39B functions as a bridge between ALYREF/THOC4 and the THO complex. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. The recruitment of the TREX complex to the intronless viral mRNA occurs via an interaction between KSHV ORF57 protein and ALYREF/THOC4.<ref>PMID:9242493</ref> <ref>PMID:11675789</ref> <ref>PMID:15833825</ref> <ref>PMID:15998806</ref> <ref>PMID:17190602</ref> <ref>PMID:17562711</ref> <ref>PMID:18974867</ref> <ref>PMID:15585580</ref> Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2 and ALYREF/THOC4.<ref>PMID:9242493</ref> <ref>PMID:11675789</ref> <ref>PMID:15833825</ref> <ref>PMID:15998806</ref> <ref>PMID:17190602</ref> <ref>PMID:17562711</ref> <ref>PMID:18974867</ref> <ref>PMID:15585580</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/t6/1t6n_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t6/1t6n_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=1t6n ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| - | <div style="background-color:#fffaf0;"> | |
| - | == Publication Abstract from PubMed == | |
| - | UAP56 is an essential eukaryotic pre-mRNA splicing factor and mRNA export factor. The mechanisms of its functions are not well understood. We determined the crystal structures of the N- and C-terminal domains of human UAP56 (comprising 90% of the full-length UAP56) at 1.9 A resolution. The two domains each have a RecA-like fold and are connected by a flexible linker. The overall fold of each domain is highly similar to the corresponding domains of eIF4A (a prototypic DExD/H-box protein), with differences at the loops and termini. This structural similarity suggests that UAP56 is likely to possess ATPase and helicase activity similar to eIF4A. The NTP binding pocket of UAP56 is occupied by a citrate ion, mimicking the phosphates of NTP and retaining the P loop in an open conformation. The crystal structure of the N-terminal domain of UAP56 also reveals a dimer interface that is potentially important for UAP56's function. | |
| - | | |
| - | Crystal structure of UAP56, a DExD/H-box protein involved in pre-mRNA splicing and mRNA export.,Zhao R, Shen J, Green MR, MacMorris M, Blumenthal T Structure. 2004 Aug;12(8):1373-81. PMID:15296731<ref>PMID:15296731</ref> | |
| - | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | </div> | |
| - | <div class="pdbe-citations 1t6n" style="background-color:#fffaf0;"></div> | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Zhao, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Pre-mrna processing protein]] | + | [[Category: Zhao R]] |
| - | [[Category: Reca-like fold]]
| + | |
| Structural highlights
Function
DX39B_HUMAN Component of the THO subcomplex of the TREX complex. The TREX complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is recruited to spliced mRNAs by a transcription-independent mechanism. Binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export. The recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. DDX39B functions as a bridge between ALYREF/THOC4 and the THO complex. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. The recruitment of the TREX complex to the intronless viral mRNA occurs via an interaction between KSHV ORF57 protein and ALYREF/THOC4.[1] [2] [3] [4] [5] [6] [7] [8] Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2 and ALYREF/THOC4.[9] [10] [11] [12] [13] [14] [15] [16]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Fleckner J, Zhang M, Valcarcel J, Green MR. U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev. 1997 Jul 15;11(14):1864-72. PMID:9242493
- ↑ Luo ML, Zhou Z, Magni K, Christoforides C, Rappsilber J, Mann M, Reed R. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature. 2001 Oct 11;413(6856):644-7. PMID:11675789 doi:http://dx.doi.org/10.1038/35098106
- ↑ Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. PMID:15833825 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-3624
- ↑ Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. PMID:15998806 doi:http://dx.doi.org/10.1101/gad.1302205
- ↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
- ↑ Shen J, Zhang L, Zhao R. Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. J Biol Chem. 2007 Aug 3;282(31):22544-50. Epub 2007 Jun 11. PMID:17562711 doi:http://dx.doi.org/10.1074/jbc.M702304200
- ↑ Boyne JR, Colgan KJ, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008 Oct;4(10):e1000194. doi: 10.1371/journal.ppat.1000194. Epub, 2008 Oct 31. PMID:18974867 doi:http://dx.doi.org/10.1371/journal.ppat.1000194
- ↑ Shi H, Cordin O, Minder CM, Linder P, Xu RM. Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. Epub 2004 Dec 7. PMID:15585580
- ↑ Fleckner J, Zhang M, Valcarcel J, Green MR. U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev. 1997 Jul 15;11(14):1864-72. PMID:9242493
- ↑ Luo ML, Zhou Z, Magni K, Christoforides C, Rappsilber J, Mann M, Reed R. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature. 2001 Oct 11;413(6856):644-7. PMID:11675789 doi:http://dx.doi.org/10.1038/35098106
- ↑ Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. PMID:15833825 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-3624
- ↑ Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. PMID:15998806 doi:http://dx.doi.org/10.1101/gad.1302205
- ↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
- ↑ Shen J, Zhang L, Zhao R. Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. J Biol Chem. 2007 Aug 3;282(31):22544-50. Epub 2007 Jun 11. PMID:17562711 doi:http://dx.doi.org/10.1074/jbc.M702304200
- ↑ Boyne JR, Colgan KJ, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008 Oct;4(10):e1000194. doi: 10.1371/journal.ppat.1000194. Epub, 2008 Oct 31. PMID:18974867 doi:http://dx.doi.org/10.1371/journal.ppat.1000194
- ↑ Shi H, Cordin O, Minder CM, Linder P, Xu RM. Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. Epub 2004 Dec 7. PMID:15585580
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