8a8r
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of TEAD4 in complex with YAP peptide== | |
| + | <StructureSection load='8a8r' size='340' side='right'caption='[[8a8r]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8a8r]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A8R FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8a8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a8r OCA], [https://pdbe.org/8a8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a8r RCSB], [https://www.ebi.ac.uk/pdbsum/8a8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a8r ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TEAD4_HUMAN TEAD4_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 non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif.<ref>PMID:18579750</ref> <ref>PMID:19324877</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The yes-associated protein (YAP) regulates the transcriptional activity of the TEAD transcription factors that are key in the control of organ morphogenesis. YAP interacts with TEAD via three secondary structure elements: a beta-strand, an alpha-helix, and an Omega-loop. Earlier results have shown that the beta-strand has only a marginal contribution in the YAP:TEAD interaction, but we show here that it significantly enhances the affinity of YAP for the Drosophila homolog of TEAD, scalloped (Sd). Nuclear magnetic resonance shows that the beta-strand adopts a more rigid conformation once bound to Sd; pre-steady state kinetic measurements show that the YAP:Sd complex is more stable. Although the crystal structures of the YAP:TEAD and YAP:Sd complexes reveal no differences at the binding interface that could explain these results, Molecular Dynamics simulations are in line with our experimental findings regarding beta-strand stability and overall binding affinity of YAP to TEAD and Sd. In particular, RMSF, correlated motion and MMGBSA analyses suggest that beta-sheet fluctuations play a relevant role in YAP(53-57) beta-strand dissociation from TEAD4 and contribute to the lower affinity of YAP for TEAD4. Identifying a clear mechanism leading to the difference in YAP's beta-strand stability proved to be challenging, pointing to the potential relevance of multiple modest structural changes or fluctuations for regulation of binding affinity. | ||
| - | + | N-terminal beta-strand in YAP is critical for stronger binding to Scalloped relative to TEAD transcription factor.,Bokhovchuk F, Mesrouze Y, Meyerhofer M, Fontana P, Zimmermann C, Villard F, Erdmann D, Kallen J, Scheufler C, Velez-Vega C, Chene P Protein Sci. 2022 Dec 15:e4545. doi: 10.1002/pro.4545. PMID:36522189<ref>PMID:36522189</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8a8r" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Kallen J]] | ||
| + | [[Category: Scheufler C]] | ||
Revision as of 09:03, 28 December 2022
Crystal structure of TEAD4 in complex with YAP peptide
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