title: Structural insights into interferon regulatory factor activation.
abstract: The interferon regulatory factors (IRFs) play important roles in development of the immune system and host defense. Recent crystallographic and biochemical studies have provided insights into the mechanism of activation of IRFs by phosphorylation. The activation of a latent closed conformation of IRF in the cytoplasm is triggered by phosphorylation of Ser/Thr residues in a C-terminal region. Phosphorylation stimulates the C-terminal autoinhibitory domain to attain a highly extended conformation triggering dimerization through extensive contacts to a second subunit. Dimers are then transported into the nucleus and assemble with the coactivator CBP/p300 to activate transcription of type I interferons and other target genes. The advances made in understanding the release of inhibition after IRF dimerization have generated a detailed structural model of how IRFs signaling pathways are activated.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA. weijun.chen@umassmed.edu
authors.forename: Weijun
authors.initials: W
authors.lastname: Chen
authors.forename: William E
authors.initials: WE
authors.lastname: Royer
mesh_terms: D050835:Interferon Regulatory Factors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010766:Phosphorylation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D050835:Interferon Regulatory Factors