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PDBsum entry 1nfa
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Transcription regulation
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PDB id
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1nfa
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References listed in PDB file
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Key reference
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Title
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Unusual rel-Like architecture in the DNA-Binding domain of the transcription factor nfatc.
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Authors
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S.A.Wolfe,
P.Zhou,
V.Dötsch,
L.Chen,
A.You,
S.N.Ho,
G.R.Crabtree,
G.Wagner,
G.L.Verdine.
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Ref.
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Nature, 1997,
385,
172-176.
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PubMed id
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Abstract
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Transcription factors of the NFAT family regulate the production of effector
proteins that coordinate the immune response. 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-kappaB 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.
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