SNAP output for PDB entry 2as5 [SNAP web server]

PDB-id

2as5; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription-DNA

Method

X-ray (2.7 Å)

Summary

Structure of the DNA binding domains of nfat and foxp2 bound specifically to DNA.

Reference

Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, Bates DL, Guo L, Han A, Ziegler SF, Mathis D, Benoist C, Chen L, Rao A (2006): "FOXP3 Controls Regulatory T Cell Function through Cooperation with NFAT." Cell(Cambridge,Mass.), 126, 375-387. doi: 10.1016/j.cell.2006.05.042.

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.