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| | ==Structure, phosphorylation and U2AF65 binding of the Nterminal Domain of splicing factor 1 during 3 splice site Recognition== | | ==Structure, phosphorylation and U2AF65 binding of the Nterminal Domain of splicing factor 1 during 3 splice site Recognition== |
| - | <StructureSection load='2m0g' size='340' side='right'caption='[[2m0g]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2m0g' size='340' side='right'caption='[[2m0g]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m0g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M0G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m0g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M0G FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SF1, ZFM1, ZNF162 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), U2AF2, U2AF65 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=2m0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m0g OCA], [https://pdbe.org/2m0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m0g RCSB], [https://www.ebi.ac.uk/pdbsum/2m0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m0g ProSAT]</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=2m0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m0g OCA], [https://pdbe.org/2m0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m0g RCSB], [https://www.ebi.ac.uk/pdbsum/2m0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m0g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> [[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>
| + | [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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bagdiul, I]] | + | [[Category: Bagdiul I]] |
| - | [[Category: Kang, H]] | + | [[Category: Kang H]] |
| - | [[Category: Kern, T]] | + | [[Category: Kern T]] |
| - | [[Category: Kraemer, A]] | + | [[Category: Kraemer A]] |
| - | [[Category: Madl, T]] | + | [[Category: Madl T]] |
| - | [[Category: Maeusbacher, N]] | + | [[Category: Maeusbacher N]] |
| - | [[Category: Sattler, M]] | + | [[Category: Sattler M]] |
| - | [[Category: Sieber, S A]] | + | [[Category: Sieber SA]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Zou, P]] | + | [[Category: Zou P]] |
| - | [[Category: Sf1]]
| + | |
| - | [[Category: Spliceosome assembly]]
| + | |
| - | [[Category: Splicing]]
| + | |
| - | [[Category: Uhm]]
| + | |
| - | [[Category: Ulm]]
| + | |
| 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
Recognition of the 3'-splice site is a key step in pre-mRNA splicing and accomplished by a dynamic complex comprising splicing factor 1 (SF1) and the U2 snRNP auxiliary factor 65-kDa subunit (U2AF65). Both proteins mediate protein-protein and protein-RNA interactions for cooperative RNA-binding during spliceosome assembly. Here, we report the solution structure of a novel helix-hairpin domain in the N-terminal region of SF1 (SF1(NTD)). The nuclear magnetic resonance- and small-angle X-ray scattering-derived structure of a complex of the SF1(NTD) with the C-terminal U2AF homology motif domain of U2AF65 (U2AF65(UHM)) reveals that, in addition to the known U2AF65(UHM)-SF1 interaction, the helix-hairpin domain forms a secondary, hydrophobic interface with U2AF65(UHM), which locks the orientation of the two subunits. Mutational analysis shows that the helix hairpin is essential for cooperative formation of the ternary SF1-U2AF65-RNA complex. We further show that tandem serine phosphorylation of a conserved Ser80-Pro81-Ser82-Pro83 motif rigidifies a long unstructured linker in the SF1 helix hairpin. Phosphorylation does not significantly alter the overall conformations of SF1, SF1-U2AF65 or the SF1-U2AF65-RNA complexes, but slightly enhances RNA binding. Our results indicate that the helix-hairpin domain of SF1 is required for cooperative 3'-splice site recognition presumably by stabilizing a unique quaternary arrangement of the SF1-U2AF65-RNA complex.
Structure, phosphorylation and U2AF65 binding of the N-terminal domain of splicing factor 1 during 3'-splice site recognition.,Zhang Y, Madl T, Bagdiul I, Kern T, Kang HS, Zou P, Mausbacher N, Sieber SA, Kramer A, Sattler M Nucleic Acids Res. 2013 Jan 1;41(2):1343-1354. Epub 2012 Nov 21. PMID:23175611[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
- ↑ Zhang Y, Madl T, Bagdiul I, Kern T, Kang HS, Zou P, Mausbacher N, Sieber SA, Kramer A, Sattler M. Structure, phosphorylation and U2AF65 binding of the N-terminal domain of splicing factor 1 during 3'-splice site recognition. Nucleic Acids Res. 2013 Jan 1;41(2):1343-1354. Epub 2012 Nov 21. PMID:23175611 doi:http://dx.doi.org/10.1093/nar/gks1097
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