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| | ==Structure of phosphorylated SF1 complex with U2AF65-UHM domain== | | ==Structure of phosphorylated SF1 complex with U2AF65-UHM domain== |
| - | <StructureSection load='4fxw' size='340' side='right' caption='[[4fxw]], [[Resolution|resolution]] 2.29Å' scene=''> | + | <StructureSection load='4fxw' size='340' side='right'caption='[[4fxw]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fxw]] is a 4 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=4FXW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FXW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fxw]] is a 4 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=4FXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FXW 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></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=4fxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fxw OCA], [https://pdbe.org/4fxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fxw RCSB], [https://www.ebi.ac.uk/pdbsum/4fxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fxw ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1opi|1opi]], [[1k1g|1k1g]], [[2g4b|2g4b]], [[4fxx|4fxx]]</td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">U2AF2, U2AF65 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), SF1, ZFM1, ZNF162 ([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=4fxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fxw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fxw RCSB], [http://www.ebi.ac.uk/pdbsum/4fxw PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/U2AF2_HUMAN U2AF2_HUMAN]] Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.<ref>PMID:15009664</ref> <ref>PMID:19470458</ref> <ref>PMID:19574390</ref> [[http://www.uniprot.org/uniprot/SF01_HUMAN SF01_HUMAN]] Necessary for the ATP-dependent first step of spliceosome assembly. Binds to the intron branch point sequence (BPS) 5'-UACUAAC-3' of the pre-mRNA. May act as transcription repressor.<ref>PMID:8752089</ref> <ref>PMID:10449420</ref> <ref>PMID:9660765</ref> | + | [https://www.uniprot.org/uniprot/U2AF2_HUMAN U2AF2_HUMAN] Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.<ref>PMID:15009664</ref> <ref>PMID:19470458</ref> <ref>PMID:19574390</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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 4fxw" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Bauer, W J]] | + | [[Category: Large Structures]] |
| - | [[Category: Kielkopf, C L]] | + | [[Category: Bauer WJ]] |
| - | [[Category: Wang, W]] | + | [[Category: Kielkopf CL]] |
| - | [[Category: Wedekind, J E]] | + | [[Category: Wang W]] |
| - | [[Category: Phosphorylation]] | + | [[Category: Wedekind JE]] |
| - | [[Category: Pre-mrna splicing factor]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Uhm]]
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| Structural highlights
Function
U2AF2_HUMAN Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.[1] [2] [3]
Publication Abstract from PubMed
The essential splicing factors U2AF(65) and SF1 cooperatively bind consensus sequences at the 3' end of introns. Phosphorylation of SF1 on a highly conserved "SPSP" motif enhances its interaction with U2AF(65) and the pre-mRNA. Here, we reveal that phosphorylation induces essential conformational changes in SF1 and in the SF1/U2AF(65)/3' splice site complex. Crystal structures of the phosphorylated (P)SF1 domain bound to the C-terminal domain of U2AF(65) at 2.29 A resolution and of the unphosphorylated SF1 domain at 2.48 A resolution demonstrate that phosphorylation induces a disorder-to-order transition within a previously unknown SF1/U2AF(65) interface. We find by small-angle X-ray scattering that the local folding of the SPSP motif transduces into global conformational changes in the nearly full-length (P)SF1/U2AF(65)/3' splice site assembly. We further determine that SPSP phosphorylation and the SF1/U2AF(65) interface are essential in vivo. These results offer a structural prototype for phosphorylation-dependent control of pre-mRNA splicing factors.
Structure of Phosphorylated SF1 Bound to U2AF(65) in an Essential Splicing Factor Complex.,Wang W, Maucuer A, Gupta A, Manceau V, Thickman KR, Bauer WJ, Kennedy SD, Wedekind JE, Green MR, Kielkopf CL Structure. 2012 Dec 22. pii: S0969-2126(12)00455-8. doi:, 10.1016/j.str.2012.10.020. PMID:23273425[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang J, Gao QS, Wang Y, Lafyatis R, Stamm S, Andreadis A. Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors. J Neurochem. 2004 Mar;88(5):1078-90. PMID:15009664
- ↑ Warf MB, Diegel JV, von Hippel PH, Berglund JA. The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9203-8. doi:, 10.1073/pnas.0900342106. Epub 2009 May 26. PMID:19470458 doi:10.1073/pnas.0900342106
- ↑ Webby CJ, Wolf A, Gromak N, Dreger M, Kramer H, Kessler B, Nielsen ML, Schmitz C, Butler DS, Yates JR 3rd, Delahunty CM, Hahn P, Lengeling A, Mann M, Proudfoot NJ, Schofield CJ, Bottger A. Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science. 2009 Jul 3;325(5936):90-3. PMID:19574390 doi:325/5936/90
- ↑ Wang W, Maucuer A, Gupta A, Manceau V, Thickman KR, Bauer WJ, Kennedy SD, Wedekind JE, Green MR, Kielkopf CL. Structure of Phosphorylated SF1 Bound to U2AF(65) in an Essential Splicing Factor Complex. Structure. 2012 Dec 22. pii: S0969-2126(12)00455-8. doi:, 10.1016/j.str.2012.10.020. PMID:23273425 doi:http://dx.doi.org/10.1016/j.str.2012.10.020
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