Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation
| Autor: | John J. Correia, Kai Lin, Rachel Delston, Hema Srinath, Suvana S. Lam, Bin Y. Qin, Rik Derynck, Cheng Liu |
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| Rok vydání: | 2003 |
| Předmět: |
Protein family
Molecular Sequence Data Static Electricity DNA-binding domain Biology Crystallography X-Ray DNA-binding protein Molecular biology Protein Structure Tertiary Cell biology DNA-Binding Proteins Transactivation Protein structure Structural Biology Humans Phosphorylation Interferon Regulatory Factor-3 Amino Acid Sequence Protein Kinases Sequence Alignment Molecular Biology Transcription factor Transcription Factors Interferon regulatory factors |
| Zdroj: | Nature Structural & Molecular Biology. 10:913-921 |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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