2AS5

Structure of the DNA binding domains of NFAT and FOXP2 bound specifically to DNA.

Summary for 2AS5

• Entry DOI: 10.2210/pdb2as5/pdb
• Related: 1a02 1owr 2a07
• Descriptor: 5'-D(TP*TP*AP*GP*GP*AP*AP*AP*AP*TP*TP*TP*GP*TP*TP*TP*CP*AP*TP*AP*GP*)-3', 5'-D(AP*AP*CP*TP*AP*TP*GP*AP*AP*AP*CP*AP*AP*AP*TP*TP*TP*TP*CP*CP*TP*)-3', Nuclear factor of activated T-cells, cytoplasmic 2, ... (6 entities in total)
• Functional Keywords: forkhead domain, rhr domain, rel homology region, ig fold, winged helix-turn-helix, b-dna, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q13469; Nucleus (Probable): O15409
• Total number of polymer chains: 8
• Total formula weight: 113024.94

Authors

Wu, Y.,Stroud, J.C.,Borde, M.,Bates, D.L.,Guo, L.,Han, A.,Rao, A.,Chen, L. (deposition date: 2005-08-22, release date: 2006-08-08, Last modification date: 2023-08-23)

Primary citation

Wu, Y.,Borde, M.,Heissmeyer, V.,Feuerer, M.,Lapan, A.D.,Stroud, J.C.,Bates, D.L.,Guo, L.,Han, A.,Ziegler, S.F.,Mathis, D.,Benoist, C.,Chen, L.,Rao, A.
FOXP3 Controls Regulatory T Cell Function through Cooperation with NFAT.
Cell(Cambridge,Mass.), 126:375-387, 2006

PubMed Abstract: 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.

PubMed: 16873067
DOI: 10.1016/j.cell.2006.05.042

Experimental method

X-RAY DIFFRACTION (2.7 Å)