1nfa

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Template:STRUCTURE 1nfa

HUMAN TRANSCRIPTION FACTOR NFATC DNA BINDING DOMAIN, NMR, 10 STRUCTURES


Overview

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.

About this Structure

1NFA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc., Wolfe SA, Zhou P, Dotsch V, Chen L, You A, Ho SN, Crabtree GR, Wagner G, Verdine GL, Nature. 1997 Jan 9;385(6612):172-6. PMID:8990122 Page seeded by OCA on Sat May 3 02:28:07 2008

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