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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/Human Human]. 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.29Å</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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1opi|1opi]], [[1k1g|1k1g]], [[2g4b|2g4b]], [[4fxx|4fxx]]</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='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 HUMAN]), SF1, ZFM1, ZNF162 ([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'>[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://pdbe.org/4fxw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fxw RCSB], [http://www.ebi.ac.uk/pdbsum/4fxw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fxw ProSAT]</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/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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[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]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Uhm]]
| + | |
| Structural highlights
Function
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.[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
- ↑ Arning S, Gruter P, Bilbe G, Kramer A. Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA. 1996 Aug;2(8):794-810. PMID:8752089
- ↑ Wang X, Bruderer S, Rafi Z, Xue J, Milburn PJ, Kramer A, Robinson PJ. Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent protein kinase regulates spliceosome assembly. EMBO J. 1999 Aug 16;18(16):4549-59. PMID:10449420 doi:http://dx.doi.org/10.1093/emboj/18.16.4549
- ↑ Zhang D, Paley AJ, Childs G. The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription. J Biol Chem. 1998 Jul 17;273(29):18086-91. PMID:9660765
- ↑ 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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