Cited by 223interferon and immune responsesDNA and Nucleic Acid ChemistryEnzyme Structure and Function

Crystal structure of an IRF‐DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences

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Fujii, Yoshifumi, Shimizu, Toshiyuki, Kusumoto, Masahiro, Kyogoku, Yoshimasa, Taniguchi, Tadatsugu, Hakoshima, Toshio·1999·The EMBO Journal

Abstract

There has been growing interest in the role of the IRF (interferon regulatory factor) family of transcription factors in the regulation of immune responses, cytokine signaling, and oncogenesis. These members are characterized by their well-conserved DNA binding domains at the N-terminal regions. Here we report the 2.2 A resolution crystal structure of the DNA binding domain of one such family member, IRF-2, bound to DNA. The structure reveals its recognition sequence, AANNGAAA (here, recognized bases are underlined and in bold, and N indicates any base), and its cooperative binding to a tandem repeat of the GAAA core sequence induced by DNA structure distortions. These facts explain well the diverse binding properties of the IRF family members, which bind to both single and tandemly repeated sequences. Furthermore, we also identified the 'helix-hairpin-strand motif' at the C terminus of the recognition helix as a metal binding site that is commonly found in certain classes of DNA-interactive proteins. Our results provide new insights into the structure and function of this family of transcription factors.

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Crossref · 10.1093/emboj/18.18.5028

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  • ICSBP associates with PU.1 and stimulates activity of the Ets/IRF composite element (EICE), which contains IRS and is present in immunoglobulin κ and λ, gp91phox, scavenger receptor, TLR-4, and IL-1β genes.

    “It also associates with PU.1 and stimulates activity of the Ets/IRF composite element (EICE), which also contains IRS and is present in the immunoglobulin (Ig) k and l , gp91 phox , scavenger receptor, toll-like receptor-4 (TLR-4), and interleukin (IL)-1 b genes. (5,23,26-30)”

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Authors
Fujii, Y., Shimizu, T., Kusumoto, M., Kyogoku, Y., Taniguchi, T., & Hakoshima, T.
Affiliations
  • Nara Institute of Science and Technology (JP)
  • Institute for Protein Research, The University of Osaka (JP)
  • The University of Tokyo (JP)
Corresponding author
Hakoshima, Toshio
Venue
The EMBO Journal
Published
1999-09-15
Volume
18
Issue
18
Pages
5028-5041
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2056627597
Cited by
223
References
92
Citations by year
2026: 8 · 2025: 9 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 7 · 2017: 8 · 2016: 10 · 2015: 6 · 2014: 5 · 2013: 13 · 2012: 4
FWCI
4.45
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Agência Nacional de Energia Elétrica
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
IRF2, interferon regulatory factors, DNA recognition sequence, cooperative DNA binding, tandem repeats, metal binding sites, protein-DNA complex, crystal structure
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Binding Sites, DNA, DNA-Binding Proteins, Metals, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Protein Conformation, Recombinant Proteins, Repressor Proteins, Transcription Factors, Sequence Homology, Amino Acid, Crystallography, X-Ray, Tandem Repeat Sequences, Macromolecular Substances, Interferon Regulatory Factor-2, Mice, In Vitro Techniques

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