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Article
Nature Structural Biology  10, 922 - 927 (2003)
Published online: 12 October 2003; | doi:10.1038/nsb1001

X-ray crystal structure of IRF-3 and its functional implications

Kiyohiro Takahasi1, Nobuo N Suzuki2, Masataka Horiuchi1, 2, Mitsuaki Mori3, Wakako Suhara3, Yasutaka Okabe3, Yukiko Fukuhara3, Hiroaki Terasawa4, Shizuo Akira5, Takashi Fujita3 & Fuyuhiko Inagaki1, 2

1  Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan.

2  CREST/JST, Kawaguchi, Japan.

3  Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8618, Japan.

4  Department of Molecular Physiology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8618, Japan.

5  Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

Correspondence should be addressed to Fuyuhiko Inagaki finagaki@pharm.hokudai.ac.jp
Transcription factor IRF-3 is post-translationally activated by Toll-like receptor (TLR) signaling and has critical roles in the regulation of innate immunity. Here we present the X-ray crystal structure of the C-terminal regulatory domain of IRF-3(175−427) (IRF-3 175C) at a resolution of 2.3 Å. IRF-3 175C is structurally similar to the Mad homology domain 2 of the Smad family. Structural and functional analyses reveal phosphorylation-induced IRF-3 dimerization, which generates an extensive acidic pocket responsible for binding with p300/CBP. Although TLR and Smad signaling are evolutionarily independent, our results suggest that IRF-3 originates from Smad and acquires its function downstream of TLR.

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Nature Structural & Molecular Biology
ISSN: 1545-9993
EISSN: 1545-9985
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