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| ==Structure of a domain-swapped FOXP3 dimer== | | ==Structure of a domain-swapped FOXP3 dimer== |
| <StructureSection load='3qrf' size='340' side='right' caption='[[3qrf]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='3qrf' size='340' side='right'caption='[[3qrf]], [[Resolution|resolution]] 2.80Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3qrf]] is a 10 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=3QRF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QRF FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3qrf]] is a 10 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=3QRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QRF FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 2.8Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a02|1a02]], [[1owr|1owr]], [[2as5|2as5]], [[2a07|2a07]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NFATC2, NFAT1, NFATP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FOXP3, IPEX, JM2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3qrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qrf OCA], [https://pdbe.org/3qrf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qrf RCSB], [https://www.ebi.ac.uk/pdbsum/3qrf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qrf ProSAT]</span></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=3qrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qrf OCA], [http://pdbe.org/3qrf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qrf RCSB], [http://www.ebi.ac.uk/pdbsum/3qrf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qrf ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Disease ==
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| [[http://www.uniprot.org/uniprot/FOXP3_HUMAN FOXP3_HUMAN]] Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome. The disease is caused by mutations affecting the gene represented in this entry.
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| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/NFAC2_HUMAN NFAC2_HUMAN]] Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway.<ref>PMID:21871017</ref> [[http://www.uniprot.org/uniprot/FOXP3_HUMAN FOXP3_HUMAN]] Probable transcription factor. Plays a critical role in the control of immune response. | | [https://www.uniprot.org/uniprot/NFAC2_HUMAN NFAC2_HUMAN] Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway.<ref>PMID:21871017</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The transcription factor FOXP3 is essential for the suppressive function of regulatory T cells that are required for maintaining self-tolerance. We have solved the crystal structure of the FOXP3 forkhead domain as a ternary complex with the DNA-binding domain of the transcription factor NFAT1 and a DNA oligonucleotide from the interleukin-2 promoter. A striking feature of this structure is that FOXP3 forms a domain-swapped dimer that bridges two molecules of DNA. Structure-guided or autoimmune disease (IPEX)-associated mutations in the domain-swap interface diminished dimer formation by the FOXP3 forkhead domain without compromising FOXP3 DNA binding. These mutations also eliminated T cell-suppressive activity conferred by FOXP3, both in vitro and in a murine model of autoimmune diabetes in vivo. We conclude that FOXP3-mediated suppressor function requires dimerization through the forkhead domain and that mutations in the dimer interface can lead to the systemic autoimmunity observed in IPEX patients.
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| Structure of a Domain-Swapped FOXP3 Dimer on DNA and Its Function in Regulatory T Cells.,Bandukwala HS, Wu Y, Feurer M, Chen Y, Barbosa B, Ghosh S, Stroud JC, Benoist C, Mathis D, Rao A, Chen L Immunity. 2011 Mar 30. PMID:21458306<ref>PMID:21458306</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3qrf" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Forkhead Box Protein 3|Forkhead Box Protein 3]] | | *[[FOX 3D structures|FOX 3D structures]] |
| *[[Forkhead box protein|Forkhead box protein]]
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Bandukwala, H S]] | | [[Category: Large Structures]] |
| [[Category: Barbosa, B]] | | [[Category: Bandukwala HS]] |
| [[Category: Benoist, C]] | | [[Category: Barbosa B]] |
| [[Category: Chen, L]] | | [[Category: Benoist C]] |
| [[Category: Chen, Y]] | | [[Category: Chen L]] |
| [[Category: Feurer, M]] | | [[Category: Chen Y]] |
| [[Category: Ghosh, S]] | | [[Category: Feurer M]] |
| [[Category: Mathis, D]] | | [[Category: Ghosh S]] |
| [[Category: Rao, A]] | | [[Category: Mathis D]] |
| [[Category: Stroud, J C]] | | [[Category: Rao A]] |
| [[Category: Wu, Y]] | | [[Category: Stroud JC]] |
| [[Category: Beta barrel]]
| | [[Category: Wu Y]] |
| [[Category: Dna binding]]
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| [[Category: Dna binding protein-dna complex]]
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| [[Category: Domain swap]]
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| [[Category: Double helix]]
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| [[Category: Forkhead domain]]
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| [[Category: Immnoglobulin fold]]
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| [[Category: Nucleus]]
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| [[Category: Protein-dna complex]]
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| [[Category: Transcription regulation]]
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