title: X-ray crystal structure of IRF-3 and its functional implications.
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 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Takahasi
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Suzuki
authors.forename: Masataka
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Mori
authors.forename: Wakako
authors.initials: W
authors.lastname: Suhara
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Okabe
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fukuhara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Terasawa
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Inagaki
mesh_terms: 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
chemical_list: 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