3kys

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{{STRUCTURE_3kys| PDB=3kys | SCENE= }}
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==Crystal structure of human YAP and TEAD complex==
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===Crystal structure of human YAP and TEAD complex===
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<StructureSection load='3kys' size='340' side='right' caption='[[3kys]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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{{ABSTRACT_PUBMED_20123905}}
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== Structural highlights ==
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<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>
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</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>
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<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>
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<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>
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</table>
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== Disease ==
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[[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>
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== Function ==
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[[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> [[http://www.uniprot.org/uniprot/YAP1_HUMAN 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).<ref>PMID:12807903</ref> <ref>PMID:17974916</ref> <ref>PMID:18579750</ref> <ref>PMID:18158288</ref> <ref>PMID:18280240</ref> <ref>PMID:21364637</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ky/3kys_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Disease==
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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<ref>PMID:20123905</ref>
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[[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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[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> [[http://www.uniprot.org/uniprot/YAP1_HUMAN 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).<ref>PMID:12807903</ref><ref>PMID:17974916</ref><ref>PMID:18579750</ref><ref>PMID:18158288</ref><ref>PMID:18280240</ref><ref>PMID:21364637</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[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].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:020123905</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Chen, F.]]
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[[Category: Chen, F]]
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[[Category: Dong, Z.]]
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[[Category: Dong, Z]]
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[[Category: Guan, K L.]]
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[[Category: Guan, K L]]
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[[Category: Li, Z.]]
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[[Category: Li, Z]]
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[[Category: Wang, P.]]
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[[Category: Wang, P]]
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[[Category: Xu, Y.]]
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[[Category: Xu, Y]]
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[[Category: Yang, H.]]
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[[Category: Yang, H]]
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[[Category: Zhao, B.]]
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[[Category: Zhao, B]]
[[Category: Activator]]
[[Category: Activator]]
[[Category: Disease mutation]]
[[Category: Disease mutation]]

Revision as of 17:32, 18 December 2014

Crystal structure of human YAP and TEAD complex

3kys, resolution 2.80Å

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