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| | <StructureSection load='4roe' size='340' side='right'caption='[[4roe]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='4roe' size='340' side='right'caption='[[4roe]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4roe]] is a 4 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=4ROE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ROE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4roe]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ROE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ROE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4roc|4roc]], [[4rod|4rod]]</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=4roe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4roe OCA], [https://pdbe.org/4roe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4roe RCSB], [https://www.ebi.ac.uk/pdbsum/4roe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4roe ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRF2, BRFU, PRO1470 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TBP, GTF2D1, TF2D, TFIID ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4roe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4roe OCA], [http://pdbe.org/4roe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4roe RCSB], [http://www.ebi.ac.uk/pdbsum/4roe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4roe ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/TBP_HUMAN TBP_HUMAN]] Defects in TBP are the cause of spinocerebellar ataxia type 17 (SCA17) [MIM:[http://omim.org/entry/607136 607136]]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA17 is an autosomal dominant cerebellar ataxia (ADCA) characterized by widespread cerebral and cerebellar atrophy, dementia and extrapyramidal signs. The molecular defect in SCA17 is the expansion of a CAG repeat in the coding region of TBP. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:11313753</ref> <ref>PMID:11448935</ref> <ref>PMID:11939898</ref> | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRF2_HUMAN BRF2_HUMAN]] General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites.<ref>PMID:11040218</ref> <ref>PMID:11121026</ref> <ref>PMID:11564744</ref> [[http://www.uniprot.org/uniprot/TBP_HUMAN TBP_HUMAN]] General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID. Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.<ref>PMID:15970593</ref> | + | [https://www.uniprot.org/uniprot/BRF2_HUMAN BRF2_HUMAN] General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites.<ref>PMID:11040218</ref> <ref>PMID:11121026</ref> <ref>PMID:11564744</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[TATA-Binding Protein|TATA-Binding Protein]] | + | *[[TATA-binding protein 3D structures|TATA-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gouge, J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Guthertz, N]] | + | [[Category: Gouge J]] |
| - | [[Category: Satia, K]] | + | [[Category: Guthertz N]] |
| - | [[Category: Vannini, A]] | + | [[Category: Satia K]] |
| - | [[Category: Transcription]]
| + | [[Category: Vannini A]] |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Function
BRF2_HUMAN General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites.[1] [2] [3]
Publication Abstract from PubMed
TFIIB-related factor 2 (Brf2) is a member of the family of TFIIB-like core transcription factors. Brf2 recruits RNA polymerase (Pol) III to type III gene-external promoters, including the U6 spliceosomal RNA and selenocysteine tRNA genes. Found only in vertebrates, Brf2 has been linked to tumorigenesis but the underlying mechanisms remain elusive. We have solved crystal structures of a human Brf2-TBP complex bound to natural promoters, obtaining a detailed view of the molecular interactions occurring at Brf2-dependent Pol III promoters and highlighting the general structural and functional conservation of human Pol II and Pol III pre-initiation complexes. Surprisingly, our structural and functional studies unravel a Brf2 redox-sensing module capable of specifically regulating Pol III transcriptional output in living cells. Furthermore, we establish Brf2 as a central redox-sensing transcription factor involved in the oxidative stress pathway and provide a mechanistic model for Brf2 genetic activation in lung and breast cancer.
Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2.,Gouge J, Satia K, Guthertz N, Widya M, Thompson AJ, Cousin P, Dergai O, Hernandez N, Vannini A Cell. 2015 Dec 3;163(6):1375-87. doi: 10.1016/j.cell.2015.11.005. PMID:26638071[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schramm L, Pendergrast PS, Sun Y, Hernandez N. Different human TFIIIB activities direct RNA polymerase III transcription from TATA-containing and TATA-less promoters. Genes Dev. 2000 Oct 15;14(20):2650-63. PMID:11040218
- ↑ Teichmann M, Wang Z, Roeder RG. A stable complex of a novel transcription factor IIB- related factor, human TFIIIB50, and associated proteins mediate selective transcription by RNA polymerase III of genes with upstream promoter elements. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14200-5. PMID:11121026 doi:http://dx.doi.org/10.1073/pnas.97.26.14200
- ↑ Cabart P, Murphy S. BRFU, a TFIIB-like factor, is directly recruited to the TATA-box of polymerase III small nuclear RNA gene promoters through its interaction with TATA-binding protein. J Biol Chem. 2001 Nov 16;276(46):43056-64. Epub 2001 Sep 19. PMID:11564744 doi:http://dx.doi.org/10.1074/jbc.M108515200
- ↑ Gouge J, Satia K, Guthertz N, Widya M, Thompson AJ, Cousin P, Dergai O, Hernandez N, Vannini A. Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2. Cell. 2015 Dec 3;163(6):1375-87. doi: 10.1016/j.cell.2015.11.005. PMID:26638071 doi:http://dx.doi.org/10.1016/j.cell.2015.11.005
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