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| | ==NMR Structure of the complex between Tfb1 subunit of TFIIH and the activation domain of VP16== | | ==NMR Structure of the complex between Tfb1 subunit of TFIIH and the activation domain of VP16== |
| - | <StructureSection load='2k2u' size='340' side='right' caption='[[2k2u]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2k2u' size='340' side='right'caption='[[2k2u]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k2u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_1 Human herpesvirus 1] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K2U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K2U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k2u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1 Human alphaherpesvirus 1] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K2U FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TFB1, YDR311W, D9740.3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), UL48 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Human herpesvirus 1])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2k2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k2u OCA], [http://pdbe.org/2k2u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k2u RCSB], [http://www.ebi.ac.uk/pdbsum/2k2u PDBsum]</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=2k2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k2u OCA], [https://pdbe.org/2k2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k2u RCSB], [https://www.ebi.ac.uk/pdbsum/2k2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k2u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TFB1_YEAST TFB1_YEAST]] Acts as component of the general transcription and DNA repair factor IIH (TFIIH) core, which is essential for both basal and activated transcription, and is involved in nucleotide excision repair (NER) of damaged DNA. TFIIH has CTD kinase and DNA-dependent ATPase activity, and is essential for polymerase II transcription in vitro.<ref>PMID:7961739</ref> <ref>PMID:8631896</ref> [[http://www.uniprot.org/uniprot/VP16_HHV1F VP16_HHV1F]] Transcriptional activator of immediate-early (IE) gene products (alpha genes). Acts as a key activator of lytic infection by initiating the lytic program through the assembly of the transcriptional regulatory VP16-induced complex composed of VP16 and two cellular factors, HCFC1 and POU2F 1. VP16-induced complex represents a regulatory switch: when it is on, it promotes IE-gene expression and thus lytic infection, and when it is off, it limits IE-gene transcription favoring latent infection (By similarity). May play a role in the aggregation of tegument proteins around nucleocapsids during virus morphogenesis. | + | [https://www.uniprot.org/uniprot/TFB1_YEAST TFB1_YEAST] Acts as component of the general transcription and DNA repair factor IIH (TFIIH) core, which is essential for both basal and activated transcription, and is involved in nucleotide excision repair (NER) of damaged DNA. TFIIH has CTD kinase and DNA-dependent ATPase activity, and is essential for polymerase II transcription in vitro.<ref>PMID:7961739</ref> <ref>PMID:8631896</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k2/2k2u_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k2/2k2u_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human herpesvirus 1]] | + | [[Category: Human alphaherpesvirus 1]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Jenkins, P M.Miller]] | + | [[Category: Di Lello P]] |
| - | [[Category: Langlois, C]] | + | [[Category: Langlois C]] |
| - | [[Category: Legault, J]] | + | [[Category: Legault J]] |
| - | [[Category: Lello, P Di]]
| + | [[Category: Mas C]] |
| - | [[Category: Mas, C]] | + | [[Category: Miller Jenkins PM]] |
| - | [[Category: Omichinski, J G]] | + | [[Category: Omichinski JG]] |
| - | [[Category: Activation]] | + | |
| - | [[Category: Dna damage]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Ph domain]]
| + | |
| - | [[Category: Protein structure complex]]
| + | |
| - | [[Category: Tfb1]]
| + | |
| - | [[Category: Tfiih]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Vp16]]
| + | |
| Structural highlights
Function
TFB1_YEAST Acts as component of the general transcription and DNA repair factor IIH (TFIIH) core, which is essential for both basal and activated transcription, and is involved in nucleotide excision repair (NER) of damaged DNA. TFIIH has CTD kinase and DNA-dependent ATPase activity, and is essential for polymerase II transcription in vitro.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Herpes Simplex Virion Protein 16 (VP16) activates transcription through a series of protein/protein interactions involving its highly acidic transactivation domain (TAD). The acidic TAD of VP16 (VP16TAD) has been shown to interact with several partner proteins both in vitro and in vivo, and many of these VP16 partners also bind the acidic TAD of the mammalian tumor suppressor protein p53. For example, the TADs of VP16 and p53 (p53TAD) both interact directly with the p62/Tfb1 (human/yeast) subunit of TFIIH, and this interaction correlates with their ability to activate both the initiation and elongation phase of transcription. In this manuscript, we use NMR spectroscopy, isothermal titration calorimetery (ITC) and site-directed mutagenesis studies to characterize the interaction between the VP16TAD and Tfb1. We identify a region within the carboxyl-terminal subdomain of the VP16TAD (VP16C) that has sequence similarity with p53TAD2 and binds Tfb1 with nanomolar affinity. We determine an NMR structure of a Tfb1/VP16C complex, which represents the first high-resolution structure of the VP16TAD in complex with a target protein. The structure demonstrates that like p53TAD2, VP16C forms a 9-residue alpha-helix in complex with Tfb1. Comparison of the VP16/Tfb1and p53/Tfb1 structures clearly demonstrates how the viral activator VP16C and p53TAD2 shares numerous aspects of binding to Tfb1. Despite the similarities, important differences are observed between the p53TAD2/Tfb1 and VP16C/Tfb1 complexes, and these differences demonstrate how selected activators such as p53 depend on phosphorylation events to selectively regulate transcription.
NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation domain of VP16: structural similarities between VP16 and p53.,Langlois C, Mas C, Di Lello P, Jenkins LM, Legault P, Omichinski JG J Am Chem Soc. 2008 Aug 13;130(32):10596-604. Epub 2008 Jul 17. PMID:18630911[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Svejstrup JQ, Feaver WJ, LaPointe J, Kornberg RD. RNA polymerase transcription factor IIH holoenzyme from yeast. J Biol Chem. 1994 Nov 11;269(45):28044-8. PMID:7961739
- ↑ Sung P, Guzder SN, Prakash L, Prakash S. Reconstitution of TFIIH and requirement of its DNA helicase subunits, Rad3 and Rad25, in the incision step of nucleotide excision repair. J Biol Chem. 1996 May 3;271(18):10821-6. PMID:8631896
- ↑ Langlois C, Mas C, Di Lello P, Jenkins LM, Legault P, Omichinski JG. NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation domain of VP16: structural similarities between VP16 and p53. J Am Chem Soc. 2008 Aug 13;130(32):10596-604. Epub 2008 Jul 17. PMID:18630911 doi:10.1021/ja800975h
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