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Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA

Nature volume 392, pages 42–48 (1998)Cite this article

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-Å-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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Figure 1: Amino-acid sequences of NFAT, NF-κB p50 and the bZIP regions of Fos and Jun.
Figure 2: The NFAT–AP-1–DNA complex (drawn with MOLSCRIPT48).
Figure 3: Superpositions of the NFAT–Fos–Jun–ARRE2 quaternary complex on the Fos–Jun–AP-1 site ternary complex (complex I of ref. 31).
Figure 4: DNA recognition in the NFAT–AP-1–ARRE2 complex.
Figure 5: The interface between NFAT and AP-1.

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Acknowledgements

We thank T. Hsieh, B. Willard and N. Sinitskaya for help with protein and DNA preparation; K. Leong, T. Stehle, J. Wang, R. Chopra and M. Jacobs for help with data collection and computation; J. Jain, G. Verdine, S. Wolfe, D. Erlanson, P. Zhou, L. Sun, B. Peterson and C. Vaughan for discussions; and L. Berman, Z. Yin and M. Soltis for synchrotron technical assistance. L.C. was supported by the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation Fellowship, and by The Medical Foundation. S.C.H. is an investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Cambridge, 02138, Massachusetts, USA

    Lin Chen, J. N. Mark Glover & Stephen C. Harrison

  2. Howard Hughes Medical Institute, Harvard University, Cambridge, 02138, Massachusetts, USA

    J. N. Mark Glover & Stephen C. Harrison

  3. Center for Blood Research, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Patrick G. Hogan & Anjana Rao

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Correspondence to Lin Chen or Stephen C. Harrison.

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Chen, L., Glover, J., Hogan, P. et al. Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 392, 42–48 (1998). https://doi.org/10.1038/32100

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