6hil - Revision history

OCA at 07:26, 26 June 2019

OCA — Wed, 26 Jun 2019 07:26:15 GMT

←Older revision		Revision as of 07:26, 26 June 2019
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	<StructureSection load='6hil' size='340' side='right'caption='[[6hil]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='6hil' size='340' side='right'caption='[[6hil]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hil]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HIL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HIL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hil]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HIL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HIL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6hik\|6hik]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6hik\|6hik]]</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>
	<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=6hil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hil OCA], [http://pdbe.org/6hil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hil RCSB], [http://www.ebi.ac.uk/pdbsum/6hil PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hil ProSAT]</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=6hil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hil OCA], [http://pdbe.org/6hil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hil RCSB], [http://www.ebi.ac.uk/pdbsum/6hil PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hil ProSAT]</span></td></tr>
	</table>		</table>
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	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kallen, J]]		[[Category: Kallen, J]]

OCA at 06:58, 3 April 2019

OCA — Wed, 03 Apr 2019 06:58:34 GMT

←Older revision		Revision as of 06:58, 3 April 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6hil is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==X-ray structure of TEAD1(Y421H mutant) complexed with YAP(wildtype): Molecular and structural characterization of a TEAD mutation at the origin of Sveinsson's chorioretinal atrophy==
		+	<StructureSection load='6hil' size='340' side='right'caption='[[6hil]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6hil]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HIL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HIL FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6hik\|6hik]]</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=6hil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hil OCA], [http://pdbe.org/6hil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hil RCSB], [http://www.ebi.ac.uk/pdbsum/6hil PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hil ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	== 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> [[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Four TEAD transcription factors (TEAD1-4) mediate the signaling output of the Hippo pathway that controls organ size in humans. TEAD transcriptional activity is regulated via interactions with the YAP, TAZ and VGLL proteins. A mutation in the TEAD1 gene, Tyr421His, has been identified in patients suffering from Sveinsson's chorioretinal atrophy (SCA), an autosomal dominant eye disease. This mutation prevents the YAP/TAZ:TEAD1 interaction. In this study, we measure the affinity of YAP, TAZ and VGLL1 for the four human TEADs and find that they have a similar affinity for all TEADs. We quantitate the effect of the mutation found in SCA patients and show that it destabilizes the YAP/TAZ:TEAD interaction by about 3 kcal/mol. We determine the structure of YAP in complex with this mutant form of TEAD and show that the histidine residue adopts different conformations at the binding interface. The presence of this flexible residue induces the destabilization of several H-bonds and the loss of van der Waals contacts, which explains why the Tyr421His(TEAD) (1) mutation has such a large destabilizing effect on the formation of the YAP:TEAD complex. This article is protected by copyright. All rights reserved.

-	~~Authors:~~ Kallen, J.	+	Molecular and structural characterization of a TEAD mutation at the origin of Sveinsson's chorioretinal atrophy.,Bokhovchuk F, Mesrouze Y, Izaac A, Meyerhofer M, Zimmermann C, Fontana P, Schmelzle T, Erdmann D, Furet P, Kallen J, Chene P FEBS J. 2019 Mar 23. doi: 10.1111/febs.14817. PMID:30903741<ref>PMID:30903741</ref>

-	~~Description: X-ray structure of TEAD1(Y421H mutant) complexed with YAP(wildtype): Molecular and structural characterization of~~ a ~~TEAD mutation at~~ the ~~origin~~ of ~~Sveinsson's chorioretinal atrophy~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6hil" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Kallen, J]]		[[Category: Kallen, J]]
		+	[[Category: Other]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription factor]]

OCA at 06:08, 26 September 2018

OCA — Wed, 26 Sep 2018 06:08:39 GMT

←Older revision		Revision as of 06:08, 26 September 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6hil is ON HOLD	+	The entry 6hil is ON HOLD until Paper Publication

	Authors: Kallen, J.		Authors: Kallen, J.

OCA: Protected "6hil" [edit=sysop:move=sysop]

OCA — Wed, 05 Sep 2018 08:49:02 GMT

Protected "6hil" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:49, 5 September 2018

OCA: New page: '''Unreleased structure''' The entry 6hil is ON HOLD Authors: Kallen, J. Description: X-ray structure of TEAD1(Y421H mutant) complexed with YAP(wildtype): Molecular and structural char...

OCA — Wed, 05 Sep 2018 08:49:00 GMT

New page: '''Unreleased structure''' The entry 6hil is ON HOLD Authors: Kallen, J. Description: X-ray structure of TEAD1(Y421H mutant) complexed with YAP(wildtype): Molecular and structural char...

New page

'''Unreleased structure'''

The entry 6hil is ON HOLD

Authors: Kallen, J.

Description: X-ray structure of TEAD1(Y421H mutant) complexed with YAP(wildtype): Molecular and structural characterization of a TEAD mutation at the origin of Sveinsson's chorioretinal atrophy
[[Category: Unreleased Structures]]
[[Category: Kallen, J]]