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| | ==Crystal Structure of the Tbox DNA binding domain of the transcription factor T-bet== | | ==Crystal Structure of the Tbox DNA binding domain of the transcription factor T-bet== |
| - | <StructureSection load='5t1j' size='340' side='right' caption='[[5t1j]], [[Resolution|resolution]] 2.95Å' scene=''> | + | <StructureSection load='5t1j' size='340' side='right'caption='[[5t1j]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t1j]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T1J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T1J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t1j]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=5T1J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T1J FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tbx21, Tbet, Tblym ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 2.947Å</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=5t1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t1j OCA], [http://pdbe.org/5t1j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t1j RCSB], [http://www.ebi.ac.uk/pdbsum/5t1j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t1j 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=5t1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t1j OCA], [https://pdbe.org/5t1j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t1j RCSB], [https://www.ebi.ac.uk/pdbsum/5t1j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t1j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TBX21_MOUSE TBX21_MOUSE]] Transcription factor that controls the expression of the TH1 cytokine, interferon-gamma. Initiates TH1 lineage development from naive TH precursor cells both by activating TH1 genetic programs and by repressing the opposing TH2 programs (By similarity). | + | [https://www.uniprot.org/uniprot/TBX21_MOUSE TBX21_MOUSE] Transcription factor that controls the expression of the TH1 cytokine, interferon-gamma. Initiates TH1 lineage development from naive TH precursor cells both by activating TH1 genetic programs and by repressing the opposing TH2 programs (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5t1j" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5t1j" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[T-box proteins|T-box proteins]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Brandt, G S]] | + | [[Category: Mus musculus]] |
| - | [[Category: Dekker, J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Glimcher, L H]] | + | [[Category: Brandt GS]] |
| - | [[Category: Hoang, Q]] | + | [[Category: Dekker J]] |
| - | [[Category: Hwang, E S]] | + | [[Category: Glimcher LH]] |
| - | [[Category: Lazarevic, V]] | + | [[Category: Hoang Q]] |
| - | [[Category: Liu, C F]] | + | [[Category: Hwang ES]] |
| - | [[Category: Naumova, N]] | + | [[Category: Lazarevic V]] |
| - | [[Category: Petsko, G A]] | + | [[Category: Liu CF]] |
| - | [[Category: Ringe, D]] | + | [[Category: Naumova N]] |
| - | [[Category: Dna binding]]
| + | [[Category: Petsko GA]] |
| - | [[Category: Dna looping]]
| + | [[Category: Ringe D]] |
| - | [[Category: Master regulator]]
| + | |
| - | [[Category: T-bet]]
| + | |
| - | [[Category: Tbox]]
| + | |
| - | [[Category: Tbx21]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| - | [[Category: Transcriptional regulation]]
| + | |
| Structural highlights
Function
TBX21_MOUSE Transcription factor that controls the expression of the TH1 cytokine, interferon-gamma. Initiates TH1 lineage development from naive TH precursor cells both by activating TH1 genetic programs and by repressing the opposing TH2 programs (By similarity).
Publication Abstract from PubMed
The transcription factor T-bet (Tbox protein expressed in T cells) is one of the master regulators of both the innate and adaptive immune responses. It plays a central role in T-cell lineage commitment, where it controls the TH1 response, and in gene regulation in plasma B-cells and dendritic cells. T-bet is a member of the Tbox family of transcription factors; however, T-bet coordinately regulates the expression of many more genes than other Tbox proteins. A central unresolved question is how T-bet is able to simultaneously recognize distant Tbox binding sites, which may be located thousands of base pairs away. We have determined the crystal structure of the Tbox DNA binding domain (DBD) of T-bet in complex with a palindromic DNA. The structure shows a quaternary structure in which the T-bet dimer has its DNA binding regions splayed far apart, making it impossible for a single dimer to bind both sites of the DNA palindrome. In contrast to most other Tbox proteins, a single T-bet DBD dimer binds simultaneously to identical half-sites on two independent DNA. A fluorescence-based assay confirms that T-bet dimers are able to bring two independent DNA molecules into close juxtaposition. Furthermore, chromosome conformation capture assays confirm that T-bet functions in the direct formation of chromatin loops in vitro and in vivo. The data are consistent with a looping/synapsing model for transcriptional regulation by T-bet in which a single dimer of the transcription factor can recognize and coalesce distinct genetic elements, either a promoter plus a distant regulatory element, or promoters on two different genes.
Crystal structure of the DNA binding domain of the transcription factor T-bet suggests simultaneous recognition of distant genome sites.,Liu CF, Brandt GS, Hoang QQ, Naumova N, Lazarevic V, Hwang ES, Dekker J, Glimcher LH, Ringe D, Petsko GA Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):E6572-E6581. Epub 2016 Oct 10. PMID:27791029[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu CF, Brandt GS, Hoang QQ, Naumova N, Lazarevic V, Hwang ES, Dekker J, Glimcher LH, Ringe D, Petsko GA. Crystal structure of the DNA binding domain of the transcription factor T-bet suggests simultaneous recognition of distant genome sites. Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):E6572-E6581. Epub 2016 Oct 10. PMID:27791029 doi:http://dx.doi.org/10.1073/pnas.1613914113
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