2x6v

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{{STRUCTURE_2x6v| PDB=2x6v | SCENE= }}
 
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===CRYSTAL STRUCTURE OF HUMAN TBX5 IN THE DNA-BOUND AND DNA-FREE FORM===
 
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{{ABSTRACT_PUBMED_20450920}}
 
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==About this Structure==
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==Crystal structure of human TBX5 in the DNA-bound and DNA-free form==
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[[2x6v]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X6V OCA].
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<StructureSection load='2x6v' size='340' side='right'caption='[[2x6v]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2x6v]] is a 4 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=2X6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X6V FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2x6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x6v OCA], [https://pdbe.org/2x6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x6v RCSB], [https://www.ebi.ac.uk/pdbsum/2x6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x6v ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/TBX5_HUMAN TBX5_HUMAN] Holt-Oram syndrome. The disease is caused by mutations affecting the gene represented in this entry. Defects in TBX5 are associated with susceptibility to dilated cardiomyopathy (DCM). A disorder characterized by ventricular and impaired systolic function, resulting in heart failure and arrhythmia. Patient are at risk of premature death.<ref>PMID:25725155</ref> <ref>PMID:25963046</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/TBX5_HUMAN TBX5_HUMAN] DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.<ref>PMID:25725155</ref> <ref>PMID:25963046</ref> <ref>PMID:8988164</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x6/2x6v_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2x6v ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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TBX5, a member of the T-box transcription factor family, plays an important role in heart and limb development. More than 60 single point or deletion mutations of human TBX5 are associated with Holt-Oram syndrome that manifests itself as heart and limb malformations in 1 out of 100,000 live births. The majority of these mutations are located in the TBX5 T-box domain. We solved the crystal structures of the human TBX5 T-box domain in its DNA-unbound form and in complex with a natural DNA target site allowing for the first time the comparison between unbound and DNA-bound forms. Our analysis identifies a 3(10)-helix at the C-terminus of the T-box domain as an inducible recognition element, critically required for the interaction with DNA, as it only forms upon DNA binding and is unstructured in the DNA-unbound form. Using circular dichroism, we characterized the thermal stability of six TBX5 mutants containing single point mutations in the T-box domain (M74V, G80R, W121G, G169R, T223M, and R237W) and compared them with wild-type protein. Mutants G80R and W121G show drastically reduced thermal stability, while the other mutants only show a marginal stability decrease. For all TBX5 mutants, binding affinities to specific and nonspecific DNA sequences were determined using isothermal titration calorimetry. All TBX5 mutants show reduced binding affinities to a specific DNA target site, although to various degrees. Interestingly, all tested TBX5 mutants differ in their ability to bind unspecific DNA, indicating that both sequence-specific and unspecific binding might contribute to the misregulation of target gene expression.
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Structural basis of TBX5-DNA recognition: the T-box domain in its DNA-bound and -unbound form.,Stirnimann CU, Ptchelkine D, Grimm C, Muller CW J Mol Biol. 2010 Jul 2;400(1):71-81. Epub 2010 May 5. PMID:20450920<ref>PMID:20450920</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2x6v" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
*[[T-box proteins|T-box proteins]]
*[[T-box proteins|T-box proteins]]
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*[[TBX5|TBX5]]
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:020450920</ref><references group="xtra"/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Grimm, C.]]
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[[Category: Large Structures]]
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[[Category: Mueller, C W.]]
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[[Category: Synthetic construct]]
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[[Category: Ptchelkine, D.]]
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[[Category: Grimm C]]
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[[Category: Stirnimann, C U.]]
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[[Category: Mueller CW]]
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[[Category: Developmental protein]]
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[[Category: Ptchelkine D]]
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[[Category: Dna-binding]]
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[[Category: Stirnimann CU]]
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[[Category: Holt-oram-syndrome]]
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[[Category: Nuclear protein]]
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[[Category: Repressor]]
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[[Category: Transcription]]
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[[Category: Transcription regulation]]
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[[Category: Transcription-dna complex]]
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Current revision

Crystal structure of human TBX5 in the DNA-bound and DNA-free form

PDB ID 2x6v

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