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An asymmetric NFAT1 dimer on a pseudo-palindromic κB-like DNA site

Nature Structural & Molecular Biology volume 10, pages 807–811 (2003)Cite this article

Abstract

The crystal structure of the NFAT1 Rel homology region (RHR) bound to a pseudo-palindromic DNA site reveals an asymmetric dimer interaction between the RHR-C domains, unrelated to the contact seen in Rel dimers such as NFκB. Binding studies with a form of the NFAT1 RHR defective in the dimer contact show loss of cooperativity and demonstrate that the same interaction is present in solution. The structure we have determined may correspond to a functional NFAT binding mode at palindromic sites of genes induced during the anergic response to weak TCR signaling.

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Figure 1: Structures of members of the RHR family of transcription factors bound to DNA.
Figure 2: View of the three crystallographically nonequivalent dimers in the orthorhombic crystal form of the NFAT1 dimer–DNA complex.
Figure 3: Dimer interface between RHR-C domains.

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Acknowledgements

We acknowledge support from US National Institutes of Health grants to S.C.H. and to A.R. CHESS is supported by the US National Science Foundation. S.C.H is an investigator of the Howard Hughes Medical Institute.

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Author notes

  1. Lin Chen

    Present address: Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado, 80309, USA

  2. Fernando Macián

    Present address: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461, USA

  3. Lei Jin and Piotr Sliz: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology and Howard Hughes Medical Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Lei Jin, Piotr Sliz, Lin Chen & Stephen C Harrison

  2. Department of Pathology, Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, 02215, Massachusetts, USA

    Fernando Macián, Anjana Rao & Patrick G Hogan

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  1. Lei Jin
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Correspondence to Stephen C Harrison.

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Jin, L., Sliz, P., Chen, L. et al. An asymmetric NFAT1 dimer on a pseudo-palindromic κB-like DNA site. Nat Struct Mol Biol 10, 807–811 (2003). https://doi.org/10.1038/nsb975

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