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| | ==TEAD DBD mutant -deltaL1== | | ==TEAD DBD mutant -deltaL1== |
| - | <StructureSection load='4z8e' size='340' side='right' caption='[[4z8e]], [[Resolution|resolution]] 2.09Å' scene=''> | + | <StructureSection load='4z8e' size='340' side='right'caption='[[4z8e]], [[Resolution|resolution]] 2.09Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4z8e]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z8E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4z8e]] is a 3 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=4Z8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z8E FirstGlance]. <br> |
| - | </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=4z8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z8e OCA], [http://pdbe.org/4z8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z8e RCSB], [http://www.ebi.ac.uk/pdbsum/4z8e PDBsum]</span></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]] 2.092Å</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=4z8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z8e OCA], [https://pdbe.org/4z8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z8e RCSB], [https://www.ebi.ac.uk/pdbsum/4z8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z8e 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> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | TEA domain (TEAD) transcription factors are essential for the normal development of eukaryotes and are the downstream effectors of the Hippo tumor suppressor pathway. Whereas our earlier work established the three-dimensional structure of the highly conserved DNA-binding domain using solution NMR spectroscopy, the structural basis for regulating the DNA-binding activity remains unknown. Here, we present the X-ray crystallographic structure and activity of a TEAD mutant containing a truncated L1 loop, DeltaL1 TEAD DBD. Unexpectedly, the three-dimensional structure of the DeltaL1 TEAD DBD reveals a helix-swapped homodimer wherein helix 1 is swapped between monomers. Furthermore, each three-helix bundle in the domain-swapped dimer is a structural homolog of MYB-like domains. Our investigations of the DNA-binding activity reveal that although the formation of the three-helix bundle by the DeltaL1 TEAD DBD is sufficient for binding to an isolated M-CAT-like DNA element, multimeric forms are deficient for cooperative binding to tandemly duplicated elements, indicating that the L1 loop contributes to the DNA-binding activity of TEAD. These results suggest that switching between monomeric and domain-swapped forms may regulate DNA selectivity of TEAD proteins.
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| - | A Potential Structural Switch for Regulating DNA-Binding by TEAD Transcription Factors.,Lee DS, Vonrhein C, Albarado D, Raman CS, Veeraraghavan S J Mol Biol. 2016 Mar 22. pii: S0022-2836(16)00194-7. doi:, 10.1016/j.jmb.2016.03.008. PMID:27016204<ref>PMID:27016204</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4z8e" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Albarado, D C]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lee, D S]] | + | [[Category: Large Structures]] |
| - | [[Category: Raman, C S]] | + | [[Category: Albarado DC]] |
| - | [[Category: Veeraraghavan, S]] | + | [[Category: Lee D-S]] |
| - | [[Category: Vonrhein, C]] | + | [[Category: Raman CS]] |
| - | [[Category: Dna binding]] | + | [[Category: Veeraraghavan S]] |
| - | [[Category: Three helix bundle]] | + | [[Category: Vonrhein C]] |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
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| 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]
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
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