2AS5: Structure Of The Dna Binding Domains Of Nfat And Foxp2 Bound Specifically To Dna

Antigen stimulation of immune cells activates the transcription factor NFAT, a key regulator of T cell activation and anergy. NFAT forms cooperative complexes with the AP-1 family of transcription factors and regulates T cell activation-associated genes. Here we show that regulatory T cell (Treg) function is mediated by an analogous cooperative complex of NFAT with the forkhead transcription factor FOXP3, a lineage specification factor for Tregs. The crystal structure of an NFAT:FOXP2:DNA complex reveals an extensive protein-protein interaction interface between NFAT and FOXP2. Structure-guided mutations of FOXP3, predicted to progressively disrupt its interaction with NFAT, interfere in a graded manner with the ability of FOXP3 to repress expression of the cytokine IL2, upregulate expression of the Treg markers CTLA4 and CD25, and confer suppressor function in a murine model of autoimmune diabetes. Thus by switching transcriptional partners, NFAT converts the acute T cell activation program into the suppressor program of Tregs.
PDB ID: 2AS5Download
MMDB ID: 86761
PDB Deposition Date: 2005/8/22
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2AS5: tetrameric; determined by author
Molecular Components in 2AS5
Label Count Molecule
Proteins (2 molecules)
Nuclear Factor of Activated T-cells, Cytoplasmic 2(Gene symbol: NFATC2)
Molecule annotation
Forkhead BOX Protein P2(Gene symbol: FOXP2)
Molecule annotation
Nucleotides(2 molecules)
5'- D(tp*tp*ap*gp*gp*ap*ap*ap*ap*tp*tp*tp*gp*tp*tp*tp*cp*ap*tp* Ap*gp*)-3'
Molecule annotation
5'- D(ap*ap*cp*tp*ap*tp*gp*ap*ap*ap*cp*ap*ap*ap*tp*tp*tp*tp*cp* Cp*tp*)-3'
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

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