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Crystal structure of IRF-3 in complex with CBP
Bin Y Qin1, Cheng Liu, Hema Srinath
1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Structure (London, England : 1993)
|September 13, 2005
Summary
Virus-induced activation of interferon beta (IFN-beta) involves IRF-3 interacting with CBP/p300. Structural analysis reveals how IRF-3
Area of Science:
- Molecular Biology
- Structural Biology
- Immunology
Background:
- Interferon beta (IFN-beta) is a crucial antiviral cytokine.
- Transcriptional activation of IFN-beta requires IRF-3 and CBP/p300 complex formation at the gene promoter.
- Understanding this interaction is key to antiviral response mechanisms.
Purpose of the Study:
- To elucidate the structural basis of IRF-3 and CBP/p300 interaction.
- To investigate the mechanism of IRF-3 activation and its subsequent binding to CBP/p300.
- To explore the conformational flexibility of CBP/p300 in response to different transcription factors.
Main Methods:
- X-ray crystallography to determine the structure of IRF-3 in complex with CBP.
- Analysis of protein-protein interaction interfaces.
- Conformational analysis of CBP/p300.
Main Results:
- The crystal structure reveals CBP binds to a hydrophobic surface on IRF-3.
- This surface is normally occluded by autoinhibitory elements in latent IRF-3.
- Virus-induced phosphorylation of IRF-3 likely causes unfolding, exposing the binding site for CBP.
- CBP can adopt different conformations based on the interacting transcription factor.
Conclusions:
- Structural insights into IRF-3 activation and CBP/p300 interaction.
- Phosphoactivation of IRF-3 exposes a binding surface for CBP.
- CBP/p300 conformation is regulated by associated transcription factors, influencing transcriptional outcomes.