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| | ==Structure of HIV Tat-specific factor 1 U2AF Homology Motif (APO-State)== | | ==Structure of HIV Tat-specific factor 1 U2AF Homology Motif (APO-State)== |
| - | <StructureSection load='6n3d' size='340' side='right' caption='[[6n3d]], [[Resolution|resolution]] 1.13Å' scene=''> | + | <StructureSection load='6n3d' size='340' side='right'caption='[[6n3d]], [[Resolution|resolution]] 1.13Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n3d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N3D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N3D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n3d]] is a 1 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=6N3D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N3D FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.13Å</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=6n3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n3d OCA], [http://pdbe.org/6n3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n3d RCSB], [http://www.ebi.ac.uk/pdbsum/6n3d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n3d ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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'>[https://proteopedia.org/fgij/fg.htm?mol=6n3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n3d OCA], [https://pdbe.org/6n3d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n3d RCSB], [https://www.ebi.ac.uk/pdbsum/6n3d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n3d 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Jenkins, J L]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kielkopf, C L]] | + | [[Category: Large Structures]] |
| - | [[Category: Loerch, S]] | + | [[Category: Jenkins JL]] |
| - | [[Category: Hiv tat-specific factor 1]] | + | [[Category: Kielkopf CL]] |
| - | [[Category: Peptide binding protein]] | + | [[Category: Loerch S]] |
| - | [[Category: Pre-mrna splicing factor]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Rna splicing factor]]
| + | |
| - | [[Category: Tat-sf1]]
| + | |
| - | [[Category: U2af homology motif]]
| + | |
| - | [[Category: U2af ligand motif]]
| + | |
| - | [[Category: Uhm]]
| + | |
| - | [[Category: Ulm]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4] [5] [6] [7] [8]
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[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Parada CA, Roeder RG. A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription. EMBO J. 1999 Jul 1;18(13):3688-701. PMID:10393184 doi:10.1093/emboj/18.13.3688
- ↑ Kim JB, Yamaguchi Y, Wada T, Handa H, Sharp PA. Tat-SF1 protein associates with RAP30 and human SPT5 proteins. Mol Cell Biol. 1999 Sep;19(9):5960-8. PMID:10454543
- ↑ Fong YW, Zhou Q. Relief of two built-In autoinhibitory mechanisms in P-TEFb is required for assembly of a multicomponent transcription elongation complex at the human immunodeficiency virus type 1 promoter. Mol Cell Biol. 2000 Aug;20(16):5897-907. PMID:10913173
- ↑ Simmons A, Aluvihare V, McMichael A. Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Immunity. 2001 Jun;14(6):763-77. PMID:11420046
- ↑ Fong YW, Zhou Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature. 2001 Dec 20-27;414(6866):929-33. PMID:11780068 doi:http://dx.doi.org/10.1038/414929a
- ↑ Misse D, Gajardo J, Oblet C, Religa A, Riquet N, Mathieu D, Yssel H, Veas F. Soluble HIV-1 gp120 enhances HIV-1 replication in non-dividing CD4+ T cells, mediated via cell signaling and Tat cofactor overexpression. AIDS. 2005 Jun 10;19(9):897-905. PMID:15905670
- ↑ Zhou Q, Sharp PA. Tat-SF1: cofactor for stimulation of transcriptional elongation by HIV-1 Tat. Science. 1996 Oct 25;274(5287):605-10. PMID:8849451
- ↑ Li XY, Green MR. The HIV-1 Tat cellular coactivator Tat-SF1 is a general transcription elongation factor. Genes Dev. 1998 Oct 1;12(19):2992-6. PMID:9765201
- ↑ Loerch S, Leach JR, Horner SW, Maji D, Jenkins JL, Pulvino M, Kielkopf CL. The pre-mRNA splicing and transcription factor Tat-SF1 is a functional partner of the spliceosome SF3b1 subunit via a U2AF homology motif interface. J Biol Chem. 2018 Dec 19. pii: RA118.006764. doi: 10.1074/jbc.RA118.006764. PMID:30567737 doi:http://dx.doi.org/10.1074/jbc.RA118.006764
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