Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA.
The nuclear factor of activated T cells (NFAT) and the AP-1 heterodimer, Fos-Jun, cooperatively bind a composite DNA site and synergistically activate the expression of many immune-response genes. A 2.7-A-resolution crystal structure of the DNA-binding domains of NFAT, Fos and Jun, in a quaternary complex with a DNA fragment containing the distal antigen-receptor response element from the interleukin-2 gene promoter, shows an extended interface between NFAT and AP-1, facilitated by the bending of Fos and DNA. The tight association of the three proteins on DNA creates a continuous groove for the recognition of 15 base pairs.
Chen
L
L
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. lchen@xta1200.harvard.edu
Glover
J N
JN
Hogan
P G
PG
Rao
A
A
Harrison
S C
SC
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011487:Protein Conformation; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry; D018808:Transcription Factor AP-1 / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA