Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA
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.
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In the NFAT-AP-1-DNA complex, NFAT and AP-1 make contacts necessary and sufficient for complex formation on DNA.
“In the NFAT-AP-1-DNA complex, the Rel homology region of NFAT and the bZip domain of AP-1 make extensive contacts with one another that are both necessary and sufficient for complex formation on DNA”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Chen et al., 1998
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Self-citation
- Authors
- Chen, L., Glover, J. N. M., Hogan, P. G., Rao, A., & Harrison, S. C.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Chen, Lin
- Harrison, Stephen C.
- Venue
- Nature
- Published
- 1998-03
- Volume
- 392
- Issue
- 6671
- Pages
- 42-48
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1847275787
- Cited by
- 521
- References
- 44
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 14 · 2023: 11 · 2022: 11 · 2021: 14 · 2020: 12 · 2019: 18 · 2018: 4 · 2017: 12 · 2016: 15 · 2015: 15 · 2014: 15 · 2013: 9 · 2012: 17
- FWCI
- 13.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- NFAT, FOS, c-Jun, DNA-binding domain, AP-1, transcription factor-DNA complex, interleukin-2 promoter, protein-DNA interactions, quaternary complex, protein-protein interfaces
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Nuclear Proteins, Protein Conformation, Recombinant Proteins, T-Lymphocytes, Transcription Factors, Transcription, Genetic, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos, Crystallography, X-Ray, Transcription Factor AP-1, NFATC Transcription Factors, Mice
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