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| | <StructureSection load='4s0h' size='340' side='right'caption='[[4s0h]], [[Resolution|resolution]] 2.82Å' scene=''> | | <StructureSection load='4s0h' size='340' side='right'caption='[[4s0h]], [[Resolution|resolution]] 2.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4s0h]] is a 8 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=4S0H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S0H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4s0h]] is a 8 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=4S0H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S0H FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TBX5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NKX2-5, CSX, NKX2.5, NKX2E ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.817Å</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=4s0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0h OCA], [http://pdbe.org/4s0h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s0h RCSB], [http://www.ebi.ac.uk/pdbsum/4s0h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0h ProSAT]</span></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=4s0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0h OCA], [https://pdbe.org/4s0h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s0h RCSB], [https://www.ebi.ac.uk/pdbsum/4s0h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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> [[http://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. | + | [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> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://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> | + | [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> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Heart development in mammalian systems is controlled by combinatorial interactions of master cardiac transcription factors such as TBX5 and NKX2.5. They bind to promoters/enhancers of downstream targets as homo- or heteromultimeric complexes. They physically interact and synergistically regulate their target genes. To elucidate the molecular basis of the intermolecular interactions, a heterodimer and a homodimer of NKX2.5 and TBX5 were studied using X-ray crystallography. Here we report a crystal structure of human NKX2.5 and TBX5 DNA binding domains in a complex with a 19 bp target DNA and a crystal structure of TBX5 homodimer. The ternary complex structure of NKX2.5 and TBX5 with the target DNA shows physical interactions between the two proteins through Lys158 (NKX2.5), Asp140 (TBX5), and Pro142 (TBX5), residues that are highly conserved in TBX and NKX families across species. Extensive homodimeric interactions were observed between the TBX5 proteins in both crystal structures. In particular, in the crystal structure of TBX5 protein that includes the N-terminal and DNA binding domains, intermolecular interactions were mediated by the N-terminal domain of the protein. The N-terminal domain of TBX5 was predicted to be "intrinsically unstructured", and in one of the two molecules in an asymmetric unit, the N-terminal domain assumes a beta-strand conformation bridging two beta-sheets from the two molecules. The structures reported here may represent general mechanisms for combinatorial interactions among transcription factors regulating developmental processes.
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| - | | + | |
| - | Intermolecular Interactions of Cardiac Transcription Factors NKX2.5 and TBX5.,Pradhan L, Gopal S, Li S, Ashur S, Suryanarayanan S, Kasahara H, Nam HJ Biochemistry. 2016 Mar 29;55(12):1702-10. doi: 10.1021/acs.biochem.6b00171. Epub , 2016 Mar 9. PMID:26926761<ref>PMID:26926761</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4s0h" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[NKX2.5 Homeodomain|NKX2.5 Homeodomain]] |
| | *[[T-box proteins|T-box proteins]] | | *[[T-box proteins|T-box proteins]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pradhan, L]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Transcription factor]] | + | [[Category: Pradhan L]] |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
Disease
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.[1] [2]
Function
TBX5_HUMAN DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.[3] [4] [5]
See Also
References
- ↑ Zhang XL, Qiu XB, Yuan F, Wang J, Zhao CM, Li RG, Xu L, Xu YJ, Shi HY, Hou XM, Qu XK, Xu YW, Yang YQ. TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy. Biochem Biophys Res Commun. 2015 Mar 27;459(1):166-71. doi:, 10.1016/j.bbrc.2015.02.094. Epub 2015 Feb 26. PMID:25725155 doi:http://dx.doi.org/10.1016/j.bbrc.2015.02.094
- ↑ Zhou W, Zhao L, Jiang JQ, Jiang WF, Yang YQ, Qiu XB. A novel TBX5 loss-of-function mutation associated with sporadic dilated cardiomyopathy. Int J Mol Med. 2015 Jul;36(1):282-8. doi: 10.3892/ijmm.2015.2206. Epub 2015 May, 11. PMID:25963046 doi:http://dx.doi.org/10.3892/ijmm.2015.2206
- ↑ Zhang XL, Qiu XB, Yuan F, Wang J, Zhao CM, Li RG, Xu L, Xu YJ, Shi HY, Hou XM, Qu XK, Xu YW, Yang YQ. TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy. Biochem Biophys Res Commun. 2015 Mar 27;459(1):166-71. doi:, 10.1016/j.bbrc.2015.02.094. Epub 2015 Feb 26. PMID:25725155 doi:http://dx.doi.org/10.1016/j.bbrc.2015.02.094
- ↑ Zhou W, Zhao L, Jiang JQ, Jiang WF, Yang YQ, Qiu XB. A novel TBX5 loss-of-function mutation associated with sporadic dilated cardiomyopathy. Int J Mol Med. 2015 Jul;36(1):282-8. doi: 10.3892/ijmm.2015.2206. Epub 2015 May, 11. PMID:25963046 doi:http://dx.doi.org/10.3892/ijmm.2015.2206
- ↑ Li QY, Newbury-Ecob RA, Terrett JA, Wilson DI, Curtis AR, Yi CH, Gebuhr T, Bullen PJ, Robson SC, Strachan T, Bonnet D, Lyonnet S, Young ID, Raeburn JA, Buckler AJ, Law DJ, Brook JD. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet. 1997 Jan;15(1):21-9. PMID:8988164 doi:http://dx.doi.org/10.1038/ng0197-21
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