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- Title
Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation.
- Authors
Qin, Bin Y; Liu, Cheng; Lam, Suvana S; Srinath, Hema; Delston, Rachel; Correia, John J; Derynck, Rik; Lin, Kai
- Abstract
IRF-3, a member of the interferon regulatory factor (IRF) family of transcription factors, functions as a molecular switch for antiviral activity. IRF-3 uses an autoinhibitory mechanism to suppress its transactivation potential in uninfected cells, and virus infection induces phosphorylation and activation of IRF-3 to initiate the antiviral responses. The crystal structure of the IRF-3 transactivation domain reveals a unique autoinhibitory mechanism, whereby the IRF association domain and the flanking autoinhibitory elements condense to form a hydrophobic core. The structure suggests that phosphorylation reorganizes the autoinhibitory elements, leading to unmasking of a hydrophobic active site and realignment of the DNA binding domain for transcriptional activation. IRF-3 exhibits marked structural and surface electrostatic potential similarity to the MH2 domain of the Smad protein family and the FHA domain, suggesting a common molecular mechanism of action among this superfamily of signaling mediators.
- Subjects
INTERFERONS; TRANSCRIPTION factors; PROTEINS
- Publication
Nature Structural Biology, 2003, Vol 10, Issue 11, p913
- ISSN
1072-8368
- Publication type
Article
- DOI
10.1038/nsb1002