1. X-ray crystal structure of IRF-3 and its functional implications
- Author
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Takahasi, Kiyohiro, Suzuki, Nobuo N, Horiuchi, Masataka, Mori, Mitsuaki, Suhara, Wakako, Okabe, Yasutaka, Fukuhara, Yukiko, Terasawa, Hiroaki, Akira, Shizuo, Fujita, Takashi, and Inagaki, Fuyuhiko
- Abstract
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.
- Published
- 2003
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