7sn6
From Proteopedia
(Difference between revisions)
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==U2AF65 UHM BOUND TO SF3B155 ULM5== | ==U2AF65 UHM BOUND TO SF3B155 ULM5== | ||
| - | <StructureSection load='7sn6' size='340' side='right'caption='[[7sn6]]' scene=''> | + | <StructureSection load='7sn6' size='340' side='right'caption='[[7sn6]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SN6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SN6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7sn6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SN6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SN6 FirstGlance]. <br> |
| - | </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=7sn6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sn6 OCA], [https://pdbe.org/7sn6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sn6 RCSB], [https://www.ebi.ac.uk/pdbsum/7sn6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sn6 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></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=7sn6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sn6 OCA], [https://pdbe.org/7sn6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sn6 RCSB], [https://www.ebi.ac.uk/pdbsum/7sn6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sn6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | During spliceosome assembly, the 3' splice site is recognized by sequential U2AF2 complexes, first with Splicing Factor 1 (SF1) and second by the SF3B1 subunit of the U2 small nuclear ribonuclear protein particle. The U2AF2-SF1 interface is well characterized, comprising a U2AF homology motif (UHM) of U2AF2 bound to a U2AF ligand motif (ULM) of SF1. However, the structure of the U2AF2-SF3B1 interface and its importance for pre-mRNA splicing are unknown. To address this knowledge gap, we determined the crystal structure of the U2AF2 UHM bound to a SF3B1 ULM site at 1.8-A resolution. We discovered a distinctive trajectory of the SF3B1 ULM across the U2AF2 UHM surface, which differs from prior UHM/ULM structures and is expected to modulate the orientations of the full-length proteins. We established that the binding affinity of the U2AF2 UHM for the cocrystallized SF3B1 ULM rivals that of a nearly full-length U2AF2 protein for an N-terminal SF3B1 region. An additional SF3B6 subunit had no detectable effect on the U2AF2-SF3B1 binding affinities. We further showed that key residues at the U2AF2 UHM-SF3B1 ULM interface contribute to coimmunoprecipitation of the splicing factors. Moreover, disrupting the U2AF2-SF3B1 interface changed splicing of representative human transcripts. From analysis of genome-wide data, we found that many of the splice sites coregulated by U2AF2 and SF3B1 differ from those coregulated by U2AF2 and SF1. Taken together, these findings support distinct structural and functional roles for the U2AF2-SF1 and U2AF2-SF3B1 complexes during the pre-mRNA splicing process. | ||
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| + | A UHM-ULM interface with unusual structural features contributes to U2AF2 and SF3B1 association for pre-mRNA splicing.,Galardi JW, Bela VN, Jeffery N, He X, Glasser E, Loerch S, Jenkins JL, Pulvino MJ, Boutz PL, Kielkopf CL J Biol Chem. 2022 Jul 1;298(8):102224. doi: 10.1016/j.jbc.2022.102224. PMID:35780835<ref>PMID:35780835</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7sn6" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Jenkins JL]] | [[Category: Jenkins JL]] | ||
[[Category: Kielkopf CL]] | [[Category: Kielkopf CL]] | ||
[[Category: Loerch S]] | [[Category: Loerch S]] | ||
Revision as of 04:15, 8 September 2022
U2AF65 UHM BOUND TO SF3B155 ULM5
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