X-ray crystal structure of IRF-3 and its functional implications
K Takahasi, NN Suzuki, M Horiuchi, M Mori… - Nature Structural & …, 2003 - nature.com
K Takahasi, NN Suzuki, M Horiuchi, M Mori, W Suhara, Y Okabe, Y Fukuhara, H Terasawa…
Nature Structural & Molecular Biology, 2003•nature.comTranscription 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 …
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 …
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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