Article abstract
Nature Structural & Molecular Biology 15, 1213 - 1220 (2008)
Published online: 5 October 2008 | doi:10.1038/nsmb.1496
Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5
Weijun Chen1, Suvana S Lam1, Hema Srinath1, Zhaozhao Jiang2, John J Correia3, Celia A Schiffer1, Katherine A Fitzgerald2, Kai Lin1,4 & William E Royer Jr1
Abstract
Interferon regulatory factors (IRFs) are essential in the innate immune response and other physiological processes. Activation of these proteins in the cytoplasm is triggered by phosphorylation of serine and threonine residues in a C-terminal autoinhibitory region, which stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/p300 and initiation of transcription. The crystal structure of the transactivation domain of pseudophosphorylated human IRF5 strikingly reveals a dimer in which the bulk of intersubunit interactions involve a highly extended C-terminal region. The corresponding region has previously been shown to block CBP/p300 binding to unphosphorylated IRF3. Mutation of key interface residues supports the observed dimer as the physiologically activated state of IRF5 and IRF3. Thus, phosphorylation is likely to activate IRF5 and other family members by triggering conformational rearrangements that switch the C-terminal segment from an autoinihibitory to a dimerization role.
- Department of Biochemistry and Molecular Pharmacology, 364 Plantation Street, Worcester, Massachusetts 01605, USA
- Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA.
- Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi 39216, USA.
- Deceased.
Correspondence to: William E Royer Jr1 e-mail: William.Royer@umassmed.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Another detour on the Toll road to the interferon antiviral responseNature Structural & Molecular Biology News and Views (01 Nov 2004)
The nuts and bolts of IRF structureNature Structural Biology News and Views (01 Nov 2003)
RESEARCH
Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivationNature Structural Biology Article (01 Nov 2003)
X-ray crystal structure of IRF-3 and its functional implicationsNature Structural Biology Article (01 Nov 2003)
See all 77 matches for Research
