5hgu

From Proteopedia

(Difference between revisions)

Revision as of 04:32, 21 September 2017

Crystal structure of human transcription factor TEAD2 in complex with palmitate

Structural highlights

5hgu is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3l15
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

TEA domain (TEAD) transcription factors bind to the coactivators YAP and TAZ and regulate the transcriptional output of the Hippo pathway, playing critical roles in organ size control and tumorigenesis. Protein S-palmitoylation attaches a fatty acid, palmitate, to cysteine residues and regulates protein trafficking, membrane localization and signaling activities. Using activity-based chemical probes, we discovered that human TEADs possess intrinsic palmitoylating enzyme-like activities and undergo autopalmitoylation at evolutionarily conserved cysteine residues under physiological conditions. We determined the crystal structures of lipid-bound TEADs and found that the lipid chain of palmitate inserts into a conserved deep hydrophobic pocket. Strikingly, palmitoylation did not alter TEAD's localization, but it was required for TEAD's binding to YAP and TAZ and was dispensable for its binding to the Vgll4 tumor suppressor. Moreover, palmitoylation-deficient TEAD mutants impaired TAZ-mediated muscle differentiation in vitro and tissue overgrowth mediated by the Drosophila YAP homolog Yorkie in vivo. Our study directly links autopalmitoylation to the transcriptional regulation of the Hippo pathway.

Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway.,Chan P, Han X, Zheng B, DeRan M, Yu J, Jarugumilli GK, Deng H, Pan D, Luo X, Wu X Nat Chem Biol. 2016 Apr;12(4):282-9. doi: 10.1038/nchembio.2036. Epub 2016 Feb, 22. PMID:26900866^[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
↑ Chan P, Han X, Zheng B, DeRan M, Yu J, Jarugumilli GK, Deng H, Pan D, Luo X, Wu X. Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway. Nat Chem Biol. 2016 Apr;12(4):282-9. doi: 10.1038/nchembio.2036. Epub 2016 Feb, 22. PMID:26900866 doi:http://dx.doi.org/10.1038/nchembio.2036

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/5hgu"

@@ Line 6: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l15|3l15]]</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=5hgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hgu OCA], [http://pdbe.org/5hgu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hgu RCSB], [http://www.ebi.ac.uk/pdbsum/5hgu 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=5hgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hgu OCA], [http://pdbe.org/5hgu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hgu RCSB], [http://www.ebi.ac.uk/pdbsum/5hgu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hgu ProSAT]</span></td></tr>
 </table>
 == Function ==

5hgu

From Proteopedia

Revision as of 04:32, 21 September 2017

Crystal structure of human transcription factor TEAD2 in complex with palmitate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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