X-ray crystal structure of IRF-3 and its functional implications.
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 A. 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.
Takahasi
Kiyohiro
K
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Suzuki
Nobuo N
NN
Horiuchi
Masataka
M
Mori
Mitsuaki
M
Suhara
Wakako
W
Okabe
Yasutaka
Y
Fukuhara
Yukiko
Y
Terasawa
Hiroaki
H
Akira
Shizuo
S
Fujita
Takashi
T
Inagaki
Fuyuhiko
F
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D050838:Interferon Regulatory Factor-3; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human