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4roc

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Revision as of 10:02, 1 May 2019

Human TFIIB-related factor 2 (Brf2) and TBP bound to U6#2 promoter

Structural highlights

4roc is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4rod, 4roe
Gene:	BRF2, BRFU, PRO1470 (HUMAN), TBP, GTF2D1, TF2D, TFIID (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TBP_HUMAN] Defects in TBP are the cause of spinocerebellar ataxia type 17 (SCA17) [MIM: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.^[1] ^[2] ^[3]

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.^[4] ^[5] ^[6] [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.^[7]

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^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zuhlke C, Hellenbroich Y, Dalski A, Kononowa N, Hagenah J, Vieregge P, Riess O, Klein C, Schwinger E. Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia. Eur J Hum Genet. 2001 Mar;9(3):160-4. PMID:11313753 doi:10.1038/sj.ejhg.5200617
↑ Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet. 2001 Jul 1;10(14):1441-8. PMID:11448935
↑ Silveira I, Miranda C, Guimaraes L, Moreira MC, Alonso I, Mendonca P, Ferro A, Pinto-Basto J, Coelho J, Ferreirinha F, Poirier J, Parreira E, Vale J, Januario C, Barbot C, Tuna A, Barros J, Koide R, Tsuji S, Holmes SE, Margolis RL, Jardim L, Pandolfo M, Coutinho P, Sequeiros J. Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. Arch Neurol. 2002 Apr;59(4):623-9. PMID:11939898
↑ 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
↑ Friedrich JK, Panov KI, Cabart P, Russell J, Zomerdijk JC. TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and stabilizes upstream binding factor at the rDNA promoter. J Biol Chem. 2005 Aug 19;280(33):29551-8. Epub 2005 Jun 21. PMID:15970593 doi:10.1074/jbc.M501595200
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4roc"

@@ Line 1: / Line 1: @@
 ==Human TFIIB-related factor 2 (Brf2) and TBP bound to U6#2 promoter==
-<StructureSection load='4roc' size='340' side='right' caption='[[4roc]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='4roc' size='340' side='right'caption='[[4roc]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4roc]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ROC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ROC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4roc]] 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=4ROC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ROC 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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rod|4rod]], [[4roe|4roe]]</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=4roc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4roc OCA], [http://pdbe.org/4roc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4roc RCSB], [http://www.ebi.ac.uk/pdbsum/4roc PDBsum]</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=4roc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4roc OCA], [http://pdbe.org/4roc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4roc RCSB], [http://www.ebi.ac.uk/pdbsum/4roc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4roc ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 22: @@
 </div>
 <div class="pdbe-citations 4roc" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Journal:Genes:1|Journal:Genes:1]]
+*[[TATA-Binding Protein|TATA-Binding Protein]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Gouge, J]]
 [[Category: Guthertz, N]]

4roc

From Proteopedia

Revision as of 10:02, 1 May 2019

Human TFIIB-related factor 2 (Brf2) and TBP bound to U6#2 promoter

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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