Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc

Scot A. Wolfe, Pei Zhou, Volker Dötsch, Lin Chen, Angie You, Steffan N. Ho, Gerald R. Crabtree, Gerhard Wagner and Gregory L. Verdine
Additional contact information
Scot A. Wolfe: Harvard University
Pei Zhou: Harvard University
Volker Dötsch: Harvard Medical School
Lin Chen: Harvard University
Angie You: Harvard University
Steffan N. Ho: Stanford University Medical School
Gerald R. Crabtree: Stanford University Medical School
Gerhard Wagner: Harvard Medical School
Gregory L. Verdine: Harvard University

Nature, 1997, vol. 385, issue 6612, 172-176

Abstract: Abstract TRANSCRIPTION factors of the NFAT family regulate the production of effector proteins that coordinate the immune response1. The immunosuppressive drugs FK506 and cyclosporin A (CsA) act by blocking a Ca2+-mediated signalling pathway leading to NFAT. Although FK506 and CsA have enabled human organs to be transplanted routinely, the toxic side-effects of these drugs limit their usage. This toxicity might be absent in antagonists that target NFAT directly. As a first step in the structure-based search for NFAT antagonists, we now report the identification and solution structure of a 20K domain of NFATc (NFATc-DBD) that is both necessary and sufficient to bind DNA and activate transcription cooperatively. Although the overall fold of the NFATc DNA-binding domain is related to that of NF-κB p50 (refs 2, 3), the two proteins use significantly different strategies for DNA recognition. On the basis of these results, we present a model for the cooperative complex formed between NFAT and the mitogenic transcription factor AP-1 on the interleukin-2 enhancer.

Date: 1997
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DOI: 10.1038/385172a0

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