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| | <StructureSection load='6n3f' size='340' side='right'caption='[[6n3f]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='6n3f' size='340' side='right'caption='[[6n3f]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n3f]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N3F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n3f]] is a 3 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=6N3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N3F FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.099Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HTATSF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=6n3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n3f OCA], [http://pdbe.org/6n3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n3f RCSB], [http://www.ebi.ac.uk/pdbsum/6n3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n3f 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=6n3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n3f OCA], [https://pdbe.org/6n3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n3f RCSB], [https://www.ebi.ac.uk/pdbsum/6n3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n3f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HTSF1_HUMAN HTSF1_HUMAN]] Functions as a general transcription factor playing a role in the process of transcriptional elongation. May mediate the reciprocal stimulatory effect of splicing on transcriptional elongation. In case of infection by HIV-1, it is up-regulated by the HIV-1 proteins NEF and gp120, acts as a cofactor required for the Tat-enhanced transcription of the virus.<ref>PMID:10393184</ref> <ref>PMID:10454543</ref> <ref>PMID:10913173</ref> <ref>PMID:11420046</ref> <ref>PMID:11780068</ref> <ref>PMID:15905670</ref> <ref>PMID:8849451</ref> <ref>PMID:9765201</ref> | + | [https://www.uniprot.org/uniprot/HTSF1_HUMAN HTSF1_HUMAN] Functions as a general transcription factor playing a role in the process of transcriptional elongation. May mediate the reciprocal stimulatory effect of splicing on transcriptional elongation. In case of infection by HIV-1, it is up-regulated by the HIV-1 proteins NEF and gp120, acts as a cofactor required for the Tat-enhanced transcription of the virus.<ref>PMID:10393184</ref> <ref>PMID:10454543</ref> <ref>PMID:10913173</ref> <ref>PMID:11420046</ref> <ref>PMID:11780068</ref> <ref>PMID:15905670</ref> <ref>PMID:8849451</ref> <ref>PMID:9765201</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The transcription elongation and pre-mRNA splicing factor Tat-SF1 associates with the U2 small nuclear ribonucleoprotein (snRNP) of the spliceosome. However, the direct binding partner and underlying interactions mediating the Tat-SF1-U2 snRNP association remain unknown. Here, we identified SF3b1 as a Tat-SF1-interacting subunit of the U2 snRNP. Our 1.1 A resolution crystal structure revealed that Tat-SF1 contains a U2AF homology motif (UHM) protein-protein interaction module. We demonstrated that Tat-SF1 preferentially and directly binds the SF3b1 subunit compared to other U2AF ligand motif (ULM)-containing splicing factors, and further established that SF3b1 association depends on the integrity of the Tat-SF1 UHM. We next compared the Tat-SF1 binding affinities for each of the five known SF3b1 ULMs and then determined the structures of representative high- and low-affinity SF3b1 ULM complexes with the Tat-SF1 UHM at 1.9 A and 2.1 A resolutions, respectively. These structures revealed a canonical UHM-ULM interface, comprising a Tat-SF1 binding pocket for a ULM tryptophan (SF3b1 W338) and electrostatic interactions with a basic ULM tail. Importantly, we found that SF3b1 regulates Tat-SF1 levels and that these two factors influence expression of overlapping representative transcripts, consistent with a functional partnership of Tat-SF1 and SF3b1. Altogether, these results define a new molecular interface of the Tat-SF1-U2 snRNP complex for gene regulation.
| + | |
| - | | + | |
| - | The pre-mRNA splicing and transcription factor Tat-SF1 is a functional partner of the spliceosome SF3b1 subunit via a U2AF homology motif interface.,Loerch S, Leach JR, Horner SW, Maji D, Jenkins JL, Pulvino M, Kielkopf CL J Biol Chem. 2018 Dec 19. pii: RA118.006764. doi: 10.1074/jbc.RA118.006764. PMID:30567737<ref>PMID:30567737</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6n3f" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jenkins, J L]] | + | [[Category: Jenkins JL]] |
| - | [[Category: Kielkopf, C L]] | + | [[Category: Kielkopf CL]] |
| - | [[Category: Leach, J R]] | + | [[Category: Leach JR]] |
| - | [[Category: Hiv tat-specific factor 1]]
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| - | [[Category: Peptide binding protein]]
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| - | [[Category: Pre-mrna splicing factor]]
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| - | [[Category: Protein-peptide complex]]
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| - | [[Category: Rna binding protein]]
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| - | [[Category: Rna splicing factor]]
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| - | [[Category: Sf3b1]]
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| - | [[Category: Tat-sf1]]
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| - | [[Category: U2af homology motif]]
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| - | [[Category: U2af ligand motif]]
| + | |
| - | [[Category: Uhm]]
| + | |
| - | [[Category: Ulm]]
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