3A77

The crystal structure of phosphorylated IRF-3

Summary for 3A77

• Entry DOI: 10.2210/pdb3a77/pdb
• Descriptor: Interferon regulatory factor 3, ACETIC ACID, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: phosphorylated protein, activator, antiviral defense, dna-binding, host-virus interaction, nucleus, phosphoprotein, transcription, transcription regulation
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q14653
• Total number of polymer chains: 4
• Total formula weight: 108422.13

Authors

Takahasi, K.,Horiuchi, M.,Noda, N.N.,Inagaki, F. (deposition date: 2009-09-17, release date: 2010-08-04, Last modification date: 2024-10-30)

Primary citation

Takahasi, K.,Horiuchi, M.,Fujii, K.,Nakamura, S.,Noda, N.N.,Yoneyama, M.,Fujita, T.,Inagaki, F.
Ser386 phosphorylation of transcription factor IRF-3 induces dimerization and association with CBP/p300 without overall conformational change.
Genes Cells, 15:901-910, 2010

PubMed 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.

PubMed: 20604809
DOI: 10.1111/j.1365-2443.2010.01427.x

Experimental method

X-RAY DIFFRACTION (1.8 Å)