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| | ==NMR structure of the DNA-binding TEA domain and insights into TEF-1 function== | | ==NMR structure of the DNA-binding TEA domain and insights into TEF-1 function== |
| - | <StructureSection load='2hzd' size='340' side='right' caption='[[2hzd]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''> | + | <StructureSection load='2hzd' size='340' side='right'caption='[[2hzd]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2hzd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HZD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HZD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2hzd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HZD FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TEAD1, TCF13, TEF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2hzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hzd OCA], [http://pdbe.org/2hzd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hzd RCSB], [http://www.ebi.ac.uk/pdbsum/2hzd 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=2hzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hzd OCA], [https://pdbe.org/2hzd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hzd RCSB], [https://www.ebi.ac.uk/pdbsum/2hzd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hzd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TEAD1_HUMAN TEAD1_HUMAN]] Defects in TEAD1 are the cause of Sveinsson chorioretinal atrophy (SCRA) [MIM:[http://omim.org/entry/108985 108985]]; also known as atrophia areata (AA) or helicoidal peripapillary chorioretinal degeneration (HPCD). SCRA is characterized by symmetrical lesions radiating from the optic disk involving the retina and the choroid.<ref>PMID:18579750</ref> <ref>PMID:20123905</ref> <ref>PMID:15016762</ref> | + | [https://www.uniprot.org/uniprot/TEAD1_HUMAN TEAD1_HUMAN] Defects in TEAD1 are the cause of Sveinsson chorioretinal atrophy (SCRA) [MIM:[https://omim.org/entry/108985 108985]; also known as atrophia areata (AA) or helicoidal peripapillary chorioretinal degeneration (HPCD). SCRA is characterized by symmetrical lesions radiating from the optic disk involving the retina and the choroid.<ref>PMID:18579750</ref> <ref>PMID:20123905</ref> <ref>PMID:15016762</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TEAD1_HUMAN TEAD1_HUMAN]] Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and cooperatively to the SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription in vivo in a cell-specific manner. The activation function appears to be mediated by a limiting cell-specific transcriptional intermediary factor (TIF). Involved in cardiac development. Binds to the M-CAT motif.<ref>PMID:18579750</ref> <ref>PMID:19324877</ref> | + | [https://www.uniprot.org/uniprot/TEAD1_HUMAN TEAD1_HUMAN] Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and cooperatively to the SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription in vivo in a cell-specific manner. The activation function appears to be mediated by a limiting cell-specific transcriptional intermediary factor (TIF). Involved in cardiac development. Binds to the M-CAT motif.<ref>PMID:18579750</ref> <ref>PMID:19324877</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/hz/2hzd_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hz/2hzd_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> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hzd ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Anbanandam, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Veeraraghavan, S]] | + | [[Category: Anbanandam A]] |
| - | [[Category: Dna-binding]] | + | [[Category: Veeraraghavan S]] |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Helix-turn-helix]]
| + | |
| Structural highlights
Disease
TEAD1_HUMAN Defects in TEAD1 are the cause of Sveinsson chorioretinal atrophy (SCRA) [MIM:108985; also known as atrophia areata (AA) or helicoidal peripapillary chorioretinal degeneration (HPCD). SCRA is characterized by symmetrical lesions radiating from the optic disk involving the retina and the choroid.[1] [2] [3]
Function
TEAD1_HUMAN Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and cooperatively to the SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription in vivo in a cell-specific manner. The activation function appears to be mediated by a limiting cell-specific transcriptional intermediary factor (TIF). Involved in cardiac development. Binds to the M-CAT motif.[4] [5]
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
Transcription enhancer factor 1 is essential for cardiac, skeletal, and smooth muscle development and uses its N-terminal TEA domain (TEAD) to bind M-CAT elements. Here, we present the first structure of TEAD and show that it is a three-helix bundle with a homeodomain fold. Structural data reveal how TEAD binds DNA. Using structure-function correlations, we find that the L1 loop is essential for cooperative loading of TEAD molecules on to tandemly duplicated M-CAT sites. Furthermore, using a microarray chip-based assay, we establish that known binding sites of the full-length protein are only a subset of DNA elements recognized by TEAD. Our results provide a model for understanding the regulation of genome-wide gene expression during development by TEA/ATTS family of transcription factors.
Insights into transcription enhancer factor 1 (TEF-1) activity from the solution structure of the TEA domain.,Anbanandam A, Albarado DC, Nguyen CT, Halder G, Gao X, Veeraraghavan S Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17225-30. Epub 2006 Nov 3. PMID:17085591[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhao B, Ye X, Yu J, Li L, Li W, Li S, Yu J, Lin JD, Wang CY, Chinnaiyan AM, Lai ZC, Guan KL. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 2008 Jul 15;22(14):1962-71. Epub 2008 Jun 25. PMID:18579750 doi:10.1101/gad.1664408
- ↑ Li Z, Zhao B, Wang P, Chen F, Dong Z, Yang H, Guan KL, Xu Y. Structural insights into the YAP and TEAD complex. Genes Dev. 2010 Feb 1;24(3):235-40. PMID:20123905 doi:24/3/235
- ↑ Fossdal R, Jonasson F, Kristjansdottir GT, Kong A, Stefansson H, Gosh S, Gulcher JR, Stefansson K. A novel TEAD1 mutation is the causative allele in Sveinsson's chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration). Hum Mol Genet. 2004 May 1;13(9):975-81. Epub 2004 Mar 11. PMID:15016762 doi:10.1093/hmg/ddh106
- ↑ Zhao B, Ye X, Yu J, Li L, Li W, Li S, Yu J, Lin JD, Wang CY, Chinnaiyan AM, Lai ZC, Guan KL. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 2008 Jul 15;22(14):1962-71. Epub 2008 Jun 25. PMID:18579750 doi:10.1101/gad.1664408
- ↑ Zhang H, Liu CY, Zha ZY, Zhao B, Yao J, Zhao S, Xiong Y, Lei QY, Guan KL. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J Biol Chem. 2009 May 15;284(20):13355-62. doi: 10.1074/jbc.M900843200. Epub 2009, Mar 26. PMID:19324877 doi:10.1074/jbc.M900843200
- ↑ Anbanandam A, Albarado DC, Nguyen CT, Halder G, Gao X, Veeraraghavan S. Insights into transcription enhancer factor 1 (TEF-1) activity from the solution structure of the TEA domain. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17225-30. Epub 2006 Nov 3. PMID:17085591
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