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3kys

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Revision as of 10:59, 9 February 2016

Crystal structure of human YAP and TEAD complex

Structural highlights

3kys 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:
Gene:	TEAD1 (HUMAN), YAP (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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] [YAP1_HUMAN] Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role 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 STK3/MST2 and STK4/MST1, 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. Plays a key role to control cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction. Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3).^[6] ^[7] ^[8] ^[9] ^[10] ^[11]

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 Yes-associated protein (YAP) transcriptional coactivator is a key regulator of organ size and a candidate human oncogene inhibited by the Hippo tumor suppressor pathway. The TEAD family of transcription factors binds directly to and mediates YAP-induced gene expression. Here we report the three-dimensional structure of the YAP (residues 50-171)-TEAD1 (residues 194-411) complex, in which YAP wraps around the globular structure of TEAD1 and forms extensive interactions via three highly conserved interfaces. Interface 3, including YAP residues 86-100, is most critical for complex formation. Our study reveals the biochemical nature of the YAP-TEAD interaction, and provides a basis for pharmacological intervention of YAP-TEAD hyperactivation in human diseases.

Structural insights into the YAP and TEAD complex.,Li Z, Zhao B, Wang P, Chen F, Dong Z, Yang H, Guan KL, Xu Y Genes Dev. 2010 Feb 1;24(3):235-40. PMID:20123905^[12]

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
↑ Komuro A, Nagai M, Navin NE, Sudol M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem. 2003 Aug 29;278(35):33334-41. Epub 2003 Jun 13. PMID:12807903 doi:10.1074/jbc.M305597200
↑ Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L, Zheng P, Ye K, Chinnaiyan A, Halder G, Lai ZC, Guan KL. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007 Nov 1;21(21):2747-61. PMID:17974916 doi:10.1101/gad.1602907
↑ 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
↑ Hao Y, Chun A, Cheung K, Rashidi B, Yang X. Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem. 2008 Feb 29;283(9):5496-509. Epub 2007 Dec 24. PMID:18158288 doi:10.1074/jbc.M709037200
↑ Levy D, Adamovich Y, Reuven N, Shaul Y. Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage. Mol Cell. 2008 Feb 15;29(3):350-61. doi: 10.1016/j.molcel.2007.12.022. PMID:18280240 doi:10.1016/j.molcel.2007.12.022
↑ Tomlinson V, Gudmundsdottir K, Luong P, Leung KY, Knebel A, Basu S. JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis. Cell Death Dis. 2010;1:e29. doi: 10.1038/cddis.2010.7. PMID:21364637 doi:10.1038/cddis.2010.7
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3kys"

@@ Line 2: / Line 2: @@
 <StructureSection load='3kys' size='340' side='right' caption='[[3kys]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3kys]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KYS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3kys]] 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=3KYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KYS FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TEAD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), YAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TEAD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), YAP ([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=3kys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kys OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kys RCSB], [http://www.ebi.ac.uk/pdbsum/3kys PDBsum]</span></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=3kys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kys OCA], [http://pdbe.org/3kys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kys RCSB], [http://www.ebi.ac.uk/pdbsum/3kys PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 19: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </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=3kys ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3kys" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Chen, F]]
 [[Category: Dong, Z]]

3kys

From Proteopedia

Revision as of 10:59, 9 February 2016

Crystal structure of human YAP and TEAD complex

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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