View source for 6wc2


==Crystal Structure of a Ternary MEF2 Chimera/NKX2-5/myocardin enhancer DNA Complex==
<StructureSection load='6wc2' size='340' side='right'caption='[[6wc2]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wc2]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WC2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</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=6wc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wc2 OCA], [https://pdbe.org/6wc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wc2 RCSB], [https://www.ebi.ac.uk/pdbsum/6wc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wc2 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NKX25_HUMAN NKX25_HUMAN] Athyreosis;Familial isolated congenital asplenia;Atrial septal defect - atrioventricular conduction defects;Atrial septal defect, ostium secundum type;Hypoplastic left heart syndrome;Tetralogy of Fallot;Familial atrial fibrillation;Familial progressive cardiac conduction defect;Thyroid hypoplasia;Ventricular septal defect. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/NKX25_HUMAN NKX25_HUMAN] Implicated in commitment to and/or differentiation of the myocardial lineage. Acts as a transcriptional activator of ANF in cooperation with GATA4 (By similarity). It is transcriptionally controlled by PBX1 and acts as a transcriptional repressor of CDKN2B (By similarity). It is required for spleen development.<ref>PMID:22560297</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MEF2 and NKX2-5 transcription factors interact with each other in cardiogenesis and are necessary for normal heart formation. Despite evidence suggesting that these two transcription factors function synergistically and possibly through direct physical interactions, molecular mechanisms by which they interact are not clear. Here we determined the crystal structures of ternary complexes of MEF2 and NKX2-5 bound to myocardin enhancer DNA in two crystal forms. These crystal structures are the first example of human MADS-box/homeobox ternary complex structures involved in cardiogenesis. Our structures reveal two possible modes of interactions between MEF2 and NKX2-5: MEF2 and NKX bind to adjacent DNA sites to recognize DNA in cis; and MEF2 and NKX bind to different DNA strands to interact with each other in trans via a conserved protein-protein interface observed in both crystal forms. Disease-related mutations are mapped to the observed protein-protein interface. Our structural studies provide a starting point to understand and further study the molecular mechanisms of the interactions between MEF2 and NKX2.5 and their roles in cardiogenesis.

Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.,Lei X, Zhao J, Sagendorf JM, Rajashekar N, Xu J, Dantas Machado AC, Sen C, Rohs R, Feng P, Chen L J Mol Biol. 2020 Sep 4;432(19):5499-5508. doi: 10.1016/j.jmb.2020.07.004. Epub, 2020 Jul 15. PMID:32681840<ref>PMID:32681840</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wc2" style="background-color:#fffaf0;"></div>

==See Also==
*[[NKX2.5 Homeodomain|NKX2.5 Homeodomain]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Chen L]]
[[Category: Lei X]]