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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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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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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DOI: https://doi.org/10.1038/32100
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