Premium
Crystal structure of ATF‐2/c‐Jun and IRF‐3 bound to the interferon‐β enhancer
Author(s) -
Panne Daniel,
Maniatis Tom,
Harrison Stephen C
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600453
Subject(s) - biology , enhancer , cooperativity , microbiology and biotechnology , binding site , dna , dna binding protein , cooperative binding , transcription factor , base pair , gene , genetics
Transcriptional activation of the interferon‐β (IFN‐β) gene requires assembly of an enhanceosome containing the transcription factors ATF‐2/c‐Jun, IRF‐3/IRF‐7, NF‐κB and HMGI(Y). These factors cooperatively bind a composite DNA site and activate expression of the IFN‐β gene. The 3.0 Å crystal structure of the DNA‐binding domains of ATF‐2/c‐Jun and two IRF‐3 molecules in a complex with 31 base pairs (bp) of the PRDIV–PRDIII region of the IFN‐β enhancer shows that association of the four proteins with DNA creates a continuous surface for the recognition of 24 bp. The structure, together with in vitro binding studies and protein mutagenesis, shows that protein–protein interactions are not critical for cooperative binding. Instead, cooperativity arises mainly through nucleotide sequence‐dependent structural changes in the DNA that allow formation of complementary DNA conformations. Because the binding sites overlap on the enhancer, the unit of recognition is the entire nucleotide sequence, not the individual subsites.