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  • The EMBO Journal (2004) 23, 4384 - 4393
  • doi:10.1038/sj.emboj.7600453

Published online: 28 October 2004

Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-bold beta enhancer

Daniel Panne1, Tom Maniatis2 and Stephen C Harrison1

  1. Department of Biological Chemistry & Molecular Pharmacology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA
  2. Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA

Correspondence to:

Stephen C Harrison, Department of Biological Chemistry & Molecular Pharmacology, Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, 02115 MA, USA. Tel.: +1 617 432 5605; Fax: +1 617 432 5607; E-mail: harrison@crystal.harvard.edu

Received 16 August 2004; Accepted 29 September 2004

Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, IRF-3/IRF-7, NF-kappaB and HMGI(Y). These factors cooperatively bind a composite DNA site and activate expression of the IFN-beta 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-beta 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.

  • Keywords:

    • ATF-2/c-Jun,
    • bZIP transcription factor,
    • IRF-3,
    • interferon-beta enhanceosome,
    • protein–DNA complex