Abstract
The Ets and IRF transcription factor families contain structurally divergent members, PU.1, Spi-B and IRF-4 (Pip), IRF-8 (ICSBP), respectively, which have evolved to cooperatively assemble on composite DNA elements and regulate gene expression in the immune system. Whereas PU.1 recruits IRF-4 or IRF-8 to DNA, it exhibits an anticooperative interaction with IRF-1 and IRF-2. We report here the structure of the ternary complex formed with the DNA binding domains of PU.1 and IRF-4 on a composite DNA element. The DNA in the complex contorts into an unusual S shape that juxtaposes PU.1 and IRF-4 for selective electrostatic and hydrophobic interactions across the central minor groove. Together, the protein-protein and protein-DNA interactions provide insights into the stereochemical basis of cooperativity and anti-cooperativity between Ets and IRF factors.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Crystallography, X-Ray
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DNA / chemistry*
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DNA / metabolism
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism
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Interferon Regulatory Factors
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Mice
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Models, Genetic
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Protein Binding
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / chemistry*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-ets
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Sequence Homology, Amino Acid
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Trans-Activators / chemistry*
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Trans-Activators / metabolism
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Transcription Factors / chemistry*
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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Interferon Regulatory Factors
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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Trans-Activators
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Transcription Factors
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interferon regulatory factor-4
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proto-oncogene protein Spi-1
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DNA