2m8d

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{{STRUCTURE_2m8d| PDB=2m8d | SCENE= }}
 
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===Structure of SRSF1 RRM2 in complex with the RNA 5'-UGAAGGAC-3'===
 
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==Function==
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==Structure of SRSF1 RRM2 in complex with the RNA 5'-UGAAGGAC-3'==
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[[http://www.uniprot.org/uniprot/SRSF1_HUMAN SRSF1_HUMAN]] Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. 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. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors.<ref>PMID:8223481</ref> <ref>PMID:8139654</ref>
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<StructureSection load='2m8d' size='340' side='right'caption='[[2m8d]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2m8d]] 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=2M8D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M8D FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2m8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m8d OCA], [https://pdbe.org/2m8d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m8d RCSB], [https://www.ebi.ac.uk/pdbsum/2m8d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m8d ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SRSF1_HUMAN SRSF1_HUMAN] Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. 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. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors.<ref>PMID:8223481</ref> <ref>PMID:8139654</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Serine/arginine (SR) proteins, one of the major families of alternative-splicing regulators in Eukarya, have two types of RNA-recognition motifs (RRMs): a canonical RRM and a pseudo-RRM. Although pseudo-RRMs are crucial for activity of SR proteins, their mode of action was unknown. By solving the structure of the human SRSF1 pseudo-RRM bound to RNA, we discovered a very unusual and sequence-specific RNA-binding mode that is centered on one alpha-helix and does not involve the beta-sheet surface, which typically mediates RNA binding by RRMs. Remarkably, this mode of binding is conserved in all pseudo-RRMs tested. Furthermore, the isolated pseudo-RRM is sufficient to regulate splicing of about half of the SRSF1 target genes tested, and the bound alpha-helix is a pivotal element for this function. Our results strongly suggest that SR proteins with a pseudo-RRM frequently regulate splicing by competing with, rather than recruiting, spliceosome components, using solely this unusual RRM.
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==About this Structure==
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Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition.,Clery A, Sinha R, Anczukow O, Corrionero A, Moursy A, Daubner GM, Valcarcel J, Krainer AR, Allain FH Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):E2802-11. doi:, 10.1073/pnas.1303445110. Epub 2013 Jul 8. PMID:23836656<ref>PMID:23836656</ref>
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[[2m8d]] 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=2M8D OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 2m8d" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Allain, F H.T.]]
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[[Category: Large Structures]]
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[[Category: Anczukow, O.]]
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[[Category: Allain FHT]]
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[[Category: Clery, A.]]
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[[Category: Anczukow O]]
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[[Category: Corrionero, A.]]
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[[Category: Clery A]]
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[[Category: Daubner, G.]]
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[[Category: Corrionero A]]
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[[Category: Krainer, A R.]]
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[[Category: Daubner G]]
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[[Category: Moursy, A.]]
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[[Category: Krainer AR]]
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[[Category: Sinha, R.]]
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[[Category: Moursy A]]
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[[Category: Valcarcel, J.]]
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[[Category: Sinha R]]
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[[Category: Pseudo-rrm]]
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[[Category: Valcarcel J]]
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[[Category: Rna binding protein-rna complex]]
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[[Category: Rrm]]
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[[Category: Sr protein]]
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Current revision

Structure of SRSF1 RRM2 in complex with the RNA 5'-UGAAGGAC-3'

PDB ID 2m8d

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