Solution structure of the core NFATC1/DNA complex.
The nuclear factor of the activated T cell (NFAT) family of transcription factors regulates cytokine gene expression by binding to the promoter/enhancer regions of antigen-responsive genes, usually in cooperation with heterologous DNA-binding partners. Here we report the solution structure of the binary complex formed between the core DNA-binding domain of human NFATC1 and the ARRE2 DNA site from the interleukin-2 promoter. The structure reveals that DNA binding induces the folding of key structural elements that are required for both sequence-specific recognition and the establishment of cooperative protein-protein contacts. The orientation of the NFAT DNA-binding domain observed in the binary NFATC1-DBD*/ DNA complex is distinct from that seen in the ternary NFATC2/AP-1/DNA complex, suggesting that the domain reorients upon formation of a cooperative transcriptional complex.
Zhou
P
P
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Sun
L J
LJ
Dötsch
V
V
Wagner
G
G
Verdine
G L
GL
D000595:Amino Acid Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D017354:Point Mutation; D011487:Protein Conformation; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; C494006:NFATC2 protein, human; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D004247:DNA