3qrf

Structure of a domain-swapped FOXP3 dimerStructure of a domain-swapped FOXP3 dimer

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. Ligands: Related: 1a02, 1owr, 2as5, 2a07 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. [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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Forkhead Box Protein 3

spinqualitylabelsall models 3qrf, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image