Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Crystallography, X-Ray
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DNA / metabolism*
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation
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Humans
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Mice
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Models, Molecular
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Molecular Sequence Data
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Mutation
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NFATC Transcription Factors
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Nuclear Proteins*
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Protein Conformation
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Proto-Oncogene Proteins c-fos / chemistry*
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Proto-Oncogene Proteins c-fos / metabolism
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Proto-Oncogene Proteins c-jun / chemistry*
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Proto-Oncogene Proteins c-jun / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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T-Lymphocytes / chemistry
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Transcription Factor AP-1 / chemistry*
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Transcription Factor AP-1 / metabolism
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic
Substances
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DNA-Binding Proteins
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NFATC Transcription Factors
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Nuclear Proteins
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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Recombinant Proteins
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Transcription Factor AP-1
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Transcription Factors
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DNA