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2leb

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Current revision

Solution structure of human SRSF2 (SC35) RRM in complex with 5'-UCCAGU-3'

Structural highlights

2leb is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2leb"

@@ Line 1: / Line 1: @@
 ==Solution structure of human SRSF2 (SC35) RRM in complex with 5'-UCCAGU-3'==
-<StructureSection load='2leb' size='340' side='right' caption='[[2leb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2leb' size='340' side='right'caption='[[2leb]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2leb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LEB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2leb]] 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=2LEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LEB FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lea|2lea]], [[2lec|2lec]]</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 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=2leb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2leb OCA], [https://pdbe.org/2leb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2leb RCSB], [https://www.ebi.ac.uk/pdbsum/2leb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2leb 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=2leb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2leb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2leb RCSB], [http://www.ebi.ac.uk/pdbsum/2leb PDBsum]</span></td></tr>
 </table>
+== 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2leb" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 20: / Line 23: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Allain, F H.T]]
+[[Category: Large Structures]]
-[[Category: Clery, A]]
+[[Category: Allain FH-T]]
-[[Category: Daubner, G M]]
+[[Category: Clery A]]
-[[Category: Jayne, S]]
+[[Category: Daubner GM]]
-[[Category: Stevenin, J]]
+[[Category: Jayne S]]
-[[Category: Rna binding protein-rna complex]]
+[[Category: Stevenin J]]
-[[Category: Rna protein complex]]
-[[Category: Splicing factor]]
-[[Category: Sr protein]]

2leb

From Proteopedia

Current revision

Solution structure of human SRSF2 (SC35) RRM in complex with 5'-UCCAGU-3'

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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