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| | ==Solution structure of human SRSF2 (SC35) RRM in complex with 5'-UGGAGU-3'== | | ==Solution structure of human SRSF2 (SC35) RRM in complex with 5'-UGGAGU-3'== |
| - | <StructureSection load='2lec' size='340' side='right'caption='[[2lec]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2lec' size='340' side='right'caption='[[2lec]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lec]] 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=2LEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LEC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lec]] 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=2LEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LEC FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2lea|2lea]], [[2leb|2leb]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SFRS2, SRSF2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lec OCA], [https://pdbe.org/2lec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lec RCSB], [https://www.ebi.ac.uk/pdbsum/2lec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lec 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=2lec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lec OCA], [https://pdbe.org/2lec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lec RCSB], [https://www.ebi.ac.uk/pdbsum/2lec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lec ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SRSF2_HUMAN SRSF2_HUMAN]] Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Binds to purine-rich RNA sequences, either 5'-AGSAGAGTA-3' (S=C or G) or 5'-GTTCGAGTA-3'. Can bind to beta-globin mRNA and commit it to the splicing pathway. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment.<ref>PMID:19592491</ref> <ref>PMID:21157427</ref>
| + | [https://www.uniprot.org/uniprot/SRSF2_HUMAN SRSF2_HUMAN] Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Binds to purine-rich RNA sequences, either 5'-AGSAGAGTA-3' (S=C or G) or 5'-GTTCGAGTA-3'. Can bind to beta-globin mRNA and commit it to the splicing pathway. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment.<ref>PMID:19592491</ref> <ref>PMID:21157427</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: Allain, F H.T]] | + | [[Category: Allain FH-T]] |
| - | [[Category: Clery, A]] | + | [[Category: Clery A]] |
| - | [[Category: Daubner, G M]] | + | [[Category: Daubner GM]] |
| - | [[Category: Jayne, S]] | + | [[Category: Jayne S]] |
| - | [[Category: Stevenin, J]] | + | [[Category: Stevenin J]] |
| - | [[Category: Rna binding protein-rna complex]]
| + | |
| - | [[Category: Rna protein complex]]
| + | |
| - | [[Category: Splicing factor]]
| + | |
| - | [[Category: Sr protein]]
| + | |
| Structural highlights
Function
SRSF2_HUMAN Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Binds to purine-rich RNA sequences, either 5'-AGSAGAGTA-3' (S=C or G) or 5'-GTTCGAGTA-3'. Can bind to beta-globin mRNA and commit it to the splicing pathway. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment.[1] [2]
Publication Abstract from PubMed
SRSF2 (SC35) is a key player in the regulation of alternative splicing events and binds degenerated RNA sequences with similar affinity in nanomolar range. We have determined the solution structure of the SRSF2 RRM bound to the 5'-UCCAGU-3' and 5'-UGGAGU-3' RNA, both identified as SRSF2 binding sites in the HIV-1 tat exon 2. RNA recognition is achieved through a novel sandwich-like structure with both termini forming a positively charged cavity to accommodate the four central nucleotides. To bind both RNA sequences equally well, SRSF2 forms a nearly identical network of intermolecular interactions by simply flipping the bases of the two consecutive C or G nucleotides into either anti or syn conformation. We validate this unusual mode of RNA recognition functionally by in-vitro and in-vivo splicing assays and propose a 5'-SSNG-3' (S=C/G) high-affinity binding consensus sequence for SRSF2. In conclusion, in addition to describe for the first time the RNA recognition mode of SRSF2, we provide the precise consensus sequence to identify new putative binding sites for this splicing factor.
A syn-anti conformational difference allows SRSF2 to recognize guanines and cytosines equally well.,Daubner GM, Clery A, Jayne S, Stevenin J, Allain FH EMBO J. 2011 Oct 14. doi: 10.1038/emboj.2011.367. PMID:22002536[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jang SW, Liu X, Fu H, Rees H, Yepes M, Levey A, Ye K. Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons. J Biol Chem. 2009 Sep 4;284(36):24512-25. doi: 10.1074/jbc.M109.026237. Epub 2009, Jul 10. PMID:19592491 doi:10.1074/jbc.M109.026237
- ↑ Edmond V, Moysan E, Khochbin S, Matthias P, Brambilla C, Brambilla E, Gazzeri S, Eymin B. Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin. EMBO J. 2011 Feb 2;30(3):510-23. doi: 10.1038/emboj.2010.333. Epub 2010 Dec 14. PMID:21157427 doi:http://dx.doi.org/10.1038/emboj.2010.333
- ↑ Daubner GM, Clery A, Jayne S, Stevenin J, Allain FH. A syn-anti conformational difference allows SRSF2 to recognize guanines and cytosines equally well. EMBO J. 2011 Oct 14. doi: 10.1038/emboj.2011.367. PMID:22002536 doi:10.1038/emboj.2011.367
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