The Structural Basis of IRF-3 Activation upon Phosphorylation.

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 pSer³⁸⁶ (pSer³⁷⁹ in mouse IRF-3) and a downstream pLxIS motif. Size-exclusion chromatography and cell-based studies show that mutations of key r

SUBMITTER: Jing T 

PROVIDER: S-EPMC7511445 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature