Structural highlights
3qrf is a 10 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Gene: | NFATC2, NFAT1, NFATP (HUMAN), FOXP3, IPEX, JM2 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[FOXP3_HUMAN] Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
[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.[1] [FOXP3_HUMAN] Probable transcription factor. Plays a critical role in the control of immune response.
Publication Abstract from PubMed
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yiu GK, Kaunisto A, Chin YR, Toker A. NFAT promotes carcinoma invasive migration through glypican-6. Biochem J. 2011 Nov 15;440(1):157-66. doi: 10.1042/BJ20110530. PMID:21871017 doi:10.1042/BJ20110530
- ↑ Bandukwala HS, Wu Y, Feurer M, Chen Y, Barbosa B, Ghosh S, Stroud JC, Benoist C, Mathis D, Rao A, Chen L. Structure of a Domain-Swapped FOXP3 Dimer on DNA and Its Function in Regulatory T Cells. Immunity. 2011 Mar 30. PMID:21458306 doi:10.1016/j.immuni.2011.02.017
