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Structure of NFAT1 bound as a dimer to the HIV-1 LTR κB element

Nature Structural & Molecular Biology volume 10, pages 800–806 (2003)Cite this article

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 κB 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 κB 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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Figure 1: Structure of the NFAT1 dimer–κB DNA complex.
Figure 2: The RHR-C dimer interface.
Figure 3: Binding of the HIV-1 LTR κB site by NFAT1.
Figure 4: E′F loop interactions.
Figure 5: Context-specific functions of the NFAT1 protein surface.

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Acknowledgements

The authors thank H. Tong from APS beamline 14-BMC, A. Han for help in data collection and G. Murphy, J. Goodrich and T. Cech for critical reading of the manuscript. This research was supported by a scholar award from the Damon Runyon–Walter Winchell Foundation and grants from the W.M. Keck Foundation and the US National Institutes of Health (L.C.).

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  1. Konstanze D von Koenig

    Present address: Institut für Biophysik und Physikalische Biochemie, Universität Regensburg, 93040, Regensburg, Germany

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, 80309-0215, Colorado, USA

    Michael J Giffin, James C Stroud, Darren L Bates, Konstanze D von Koenig, John Hardin & Lin Chen

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Giffin, M., Stroud, J., Bates, D. et al. Structure of NFAT1 bound as a dimer to the HIV-1 LTR κB element. Nat Struct Mol Biol 10, 800–806 (2003). https://doi.org/10.1038/nsb981

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