Structure of NFAT1 bound as a dimer to the HIV-1 LTR κB element
Abstract
DNA binding by NFAT1 as a dimer has been implicated in the activation of host and viral genes. Here we report a crystal structure of NFAT1 bound cooperatively as a dimer to the highly conserved kappa B site from the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR). This structure reveals a new mode of dimerization and protein-DNA recognition by the Rel homology region (RHR) of NFAT1. The two NFAT1 monomers form a complete circle around the kappa B DNA through protein-protein interactions mediated by both their N- and C-terminal subdomains. The major dimer interface, formed by the C-terminal domain, is asymmetric and substantially different from the symmetric dimer interface seen in other Rel family proteins. Comparison to other NFAT structures, including NFAT5 and the NFAT1-Fos-Jun-ARRE2 complex, reveals that NFAT1 adopts different conformations and its protein surfaces mediate distinct protein-protein interactions in the context of different DNA sites.
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Structural analysis places NFATc2 T483 in the REL-homology region, T483 and T733 close to the DNA binding surface, and T862, T870, and T893 in the flexible C-terminal region associated with NFATc2 translocation.
“Analysis of publicly available crystal structures of NFATc2 revealed that T483 is located in the REL-homology region (aa 408–677), T483 and T733 are located close to the DNA binding surface (PDB: 1P7H and 1OWR) (40), and the remaining three threonine (T862, T870, and T893) are present in the flexible C-terminal region (aa 678–925) associated with NFATc2 translocation (Fig. 6A) (41).”
From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [40]
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References 48 · Cited by 102
- Authors
- Giffin, M. J., Stroud, J. C., Bates, D. L., von Koenig, K. D., Hardin, J., & Chen, L.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Chen, Lin
- Venue
- Nature Structural & Molecular Biology
- Published
- 2003-08-31
- Volume
- 10
- Issue
- 10
- Pages
- 800-806
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2138821254
- Cited by
- 102
- References
- 48
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2022: 1 · 2021: 5 · 2020: 9 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM064642, T32GM008759, T32GM142607)
- National Institute of Allergy and Infectious Diseases (R21AI049905)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- NFAT1, HIV-1 long terminal repeat, protein dimerization, protein-DNA recognition, crystal structure, C-terminal domain, Rel family transcription factors, transcriptional activation
- MeSH terms
- Amino Acid Sequence, DNA-Binding Proteins, Humans, Molecular Sequence Data, Nuclear Proteins, Transcription Factors, HIV Long Terminal Repeat, Protein Structure, Tertiary, Dimerization, NFATC Transcription Factors
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