Ser386 phosphorylation of transcription factor IRF‐3 induces dimerization and association with CBP/p300 without overall conformational change |
| |
| Authors: | Kiyohiro Takahasi Masataka Horiuchi Kiyonaga Fujii Shingo Nakamura Nobuo N Noda Mitsutoshi Yoneyama Takashi Fujita Fuyuhiko Inagaki |
| |
| Affiliation: | 1. Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N‐12, W‐6, Kita‐ku, Sapporo 060‐0812, Japan;2. Present address: Institute for Innovative NanoBio Drug Discovery and Development, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606‐8507, Japan.;3. Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto 606‐8507, Japan;4. Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606‐8507, Japan;5. PRESTO, Japan Science and Technology Agency, 4‐1‐8 Honcho Kawaguchi, Saitama 332‐0012, Japan |
| |
| Abstract: | The transcription factor IRF‐3 is activated by microbial invasions and produces a variety of cytokines including type‐I interferon. Upon microbial infection, IRF‐3 is phosphorylated at its C‐terminal regulatory domain, then oligomerized, translocated into the nucleus, and here it binds to CBP/p300. Although a number of studies have been reported investigating the activation mechanism of IRF‐3, there are a number of unresolved issues, especially on the phosphorylation sites, the oligomerization process and the binding mechanism with CBP/p300. In this report, the phosphorylated IRF‐3 regulatory domain (IRF‐3 RD) was prepared using the kinase IKK‐i, and the active form of phosphorylated IRF‐3 RD was identified. The paper also reports the crystal structure of the active form of the phosphorylated IRF‐3 RD. Furthermore, the phosphorylation of Ser386 was found to be essential for its dimerization and binding with CBP/p300 using mutational analysis and mass spectrometry. Thus, we conclude that the phosphorylation of Ser386 is essential for activation of IRF‐3. |
| |
| Keywords: | |
|
|
