2m09: Difference between revisions

Revision as of 13:21, 22 February 2023

Structure, phosphorylation and U2AF65 binding of the Nterminal Domain of splicing factor 1 during 3 splice site Recognition

Structural highlights

2m09 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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:https://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:https://dx.doi.org/10.1093/nar/gks1097

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/10.1093/emboj/18.16.4549

[3] 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

[4] 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:https://dx.doi.org/10.1093/nar/gks1097

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[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 ==Structure, phosphorylation and U2AF65 binding of the Nterminal Domain of splicing factor 1 during 3 splice site Recognition==
-<StructureSection load='2m09' size='340' side='right'caption='[[2m09]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='2m09' size='340' side='right'caption='[[2m09]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2m09]] is a 1 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=2M09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M09 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2m09]] is a 1 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=2M09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M09 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])</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=2m09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m09 OCA], [https://pdbe.org/2m09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m09 RCSB], [https://www.ebi.ac.uk/pdbsum/2m09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m09 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=2m09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m09 OCA], [https://pdbe.org/2m09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m09 RCSB], [https://www.ebi.ac.uk/pdbsum/2m09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m09 ProSAT]</span></td></tr>
 </table>
 == 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/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;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[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: Rrm]]
-[[Category: Sf1]]
-[[Category: Spliceosome assembly]]
-[[Category: Transcription]]
-[[Category: Uhm]]
-[[Category: Ulm]]

2m09: Difference between revisions

Revision as of 13:21, 22 February 2023

Structure, phosphorylation and U2AF65 binding of the Nterminal Domain of splicing factor 1 during 3 splice site Recognition

Structural highlights

Function

Publication Abstract from PubMed

References

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