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5emv

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Revision as of 07:05, 22 April 2020

Crystal structure of the palmitoylated human TEAD2 transcription factor

Structural highlights

5emv is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	5emw
Gene:	TEAD2, TEF4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TEAD2_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 to the SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3'). May be involved in the gene regulation of neural development. Binds to the M-CAT motif.^[1] ^[2]

Publication Abstract from PubMed

The Hippo signaling pathway is responsible for regulating the function of TEAD family transcription factors in metazoans. TEADs, with their co-activators YAP/TAZ, are critical for controlling cell differentiation and organ size through their transcriptional activation of genes involved in cell growth and proliferation. Dysregulation of the Hippo pathway has been implicated in multiple forms of cancer. Here, we identify a novel form of regulation of TEAD family proteins. We show that human TEADs are palmitoylated at a universally conserved cysteine, and report the crystal structures of the human TEAD2 and TEAD3 YAP-binding domains in their palmitoylated forms. These structures show a palmitate bound within a highly conserved hydrophobic cavity at each protein's core. Our findings also demonstrate that this modification is required for proper TEAD folding and stability, indicating a potential new avenue for pharmacologically regulating the Hippo pathway through the modulation of TEAD palmitoylation.

Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling.,Noland CL, Gierke S, Schnier PD, Murray J, Sandoval WN, Sagolla M, Dey A, Hannoush RN, Fairbrother WJ, Cunningham CN Structure. 2016 Jan 5;24(1):179-86. doi: 10.1016/j.str.2015.11.005. Epub 2015 Dec, 24. PMID:26724994^[3]

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
↑ 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
↑ Noland CL, Gierke S, Schnier PD, Murray J, Sandoval WN, Sagolla M, Dey A, Hannoush RN, Fairbrother WJ, Cunningham CN. Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling. Structure. 2016 Jan 5;24(1):179-86. doi: 10.1016/j.str.2015.11.005. Epub 2015 Dec, 24. PMID:26724994 doi:http://dx.doi.org/10.1016/j.str.2015.11.005

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5emv"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the palmitoylated human TEAD2 transcription factor==
-<StructureSection load='5emv' size='340' side='right' caption='[[5emv]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5emv' size='340' side='right'caption='[[5emv]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5emv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EMV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EMV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5emv]] is a 2 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=5EMV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EMV FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=P1L:S-PALMITOYL-L-CYSTEINE'>P1L</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5emw|5emw]]</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=5emv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5emv OCA], [http://pdbe.org/5emv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5emv RCSB], [http://www.ebi.ac.uk/pdbsum/5emv PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TEAD2, TEF4 ([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://proteopedia.org/fgij/fg.htm?mol=5emv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5emv OCA], [http://pdbe.org/5emv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5emv RCSB], [http://www.ebi.ac.uk/pdbsum/5emv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5emv ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Cunningham, C N]]
 [[Category: Dey, A]]

5emv

From Proteopedia

Revision as of 07:05, 22 April 2020

Crystal structure of the palmitoylated human TEAD2 transcription factor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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