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.
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Acknowledgements
This work was supported by grant-in-aids for CREST of Japan Science and Technology, Scientific Research on Priority Areas and National Project on Protein Structural and Functional Analyses from the Ministry of Education, Culture, Sports, Science and Technology, Japan to F.I.
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Takahasi, K., Suzuki, N., Horiuchi, M. et al. X-ray crystal structure of IRF-3 and its functional implications. Nat Struct Mol Biol 10, 922–927 (2003). https://doi.org/10.1038/nsb1001
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DOI: https://doi.org/10.1038/nsb1001
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