Structural highlights
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 PubMedThe 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 AlsoReferences
| ||||||||||||||||||||||
This page was last modified 06:20, 8 June 2022.