7JFL

Crystal structure of human phosphorylated IRF-3 bound to CBP

Summary for 7JFL

• Entry DOI: 10.2210/pdb7jfl/pdb
• Descriptor: Interferon regulatory factor 3, CREB-binding protein (3 entities in total)
• Functional Keywords: transcription factor, phosphorylation, innate immunity, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 58090.01

Authors

Li, P.,Jing, T.,Zhao, B. (deposition date: 2020-07-17, release date: 2020-09-09, Last modification date: 2023-10-18)

Primary citation

Jing, T.,Zhao, B.,Xu, P.,Gao, X.,Chi, L.,Han, H.,Sankaran, B.,Li, P.
The Structural Basis of IRF-3 Activation upon Phosphorylation.
J Immunol., 205:1886-1896, 2020

PubMed Abstract: The innate immune system is the first line of defense against bacterial and viral infections. The recognition of pathogen-associated molecular patterns by the RIG-I-like receptors, TLRs, and cGAS leads to the induction of IFN-I by activating the transcription factor IRF-3. Although the mechanism of IRF-3 activation has been extensively studied, the structural basis of IRF-3 activation upon phosphorylation is not fully understood. In this study, we determined the crystal structures of phosphorylated human and mouse IRF-3 bound to CREB-binding protein (CBP), which reveal that phosphorylated IRF-3 forms a dimer via pSer (pSer in mouse IRF-3) and a downstream LIS motif. Size-exclusion chromatography and cell-based studies show that mutations of key residues interacting with pSer severely impair IRF-3 activation and IFN-β induction. By contrast, phosphorylation of Ser within the LIS motif of human IRF-3 only plays a moderate role in IRF-3 activation. The mouse IRF-3/CBP complex structure reveals that the mechanism of mouse IRF-3 activation is similar but distinct from human IRF-3. These structural and functional studies reveal the detailed mechanism of IRF-3 activation upon phosphorylation.

PubMed: 32826280
DOI: 10.4049/jimmunol.2000026

Experimental method

X-RAY DIFFRACTION (1.68 Å)