5JEM

Complex of IRF-3 with CBP

5JEM の概要

• エントリーDOI: 10.2210/pdb5jem/pdb
• 関連するPDBエントリー: 5JEJ 5JEK 5JEL 5JEO 5JER
• 分子名称: Interferon regulatory factor 3, CREB-binding protein (3 entities in total)
• 機能のキーワード: innate immunity, signaling, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : Q14653 Q92793
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 116196.38

構造登録者

Zhao, B.,Li, P. (登録日: 2016-04-18, 公開日: 2016-06-15, 最終更新日: 2024-03-06)

主引用文献

Zhao, B.,Shu, C.,Gao, X.,Sankaran, B.,Du, F.,Shelton, C.L.,Herr, A.B.,Ji, J.Y.,Li, P.
Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins.
Proc.Natl.Acad.Sci.USA, 113:E3403-E3412, 2016

PubMed Abstract: Type I IFNs are key cytokines mediating innate antiviral immunity. cGMP-AMP synthase, ritinoic acid-inducible protein 1 (RIG-I)-like receptors, and Toll-like receptors recognize microbial double-stranded (ds)DNA, dsRNA, and LPS to induce the expression of type I IFNs. These signaling pathways converge at the recruitment and activation of the transcription factor IRF-3 (IFN regulatory factor 3). The adaptor proteins STING (stimulator of IFN genes), MAVS (mitochondrial antiviral signaling), and TRIF (TIR domain-containing adaptor inducing IFN-β) mediate the recruitment of IRF-3 through a conserved pLxIS motif. Here we show that the pLxIS motif of phosphorylated STING, MAVS, and TRIF binds to IRF-3 in a similar manner, whereas residues upstream of the motif confer specificity. The structure of the IRF-3 phosphomimetic mutant S386/396E bound to the cAMP response element binding protein (CREB)-binding protein reveals that the pLxIS motif also mediates IRF-3 dimerization and activation. Moreover, rotavirus NSP1 (nonstructural protein 1) employs a pLxIS motif to target IRF-3 for degradation, but phosphorylation of NSP1 is not required for its activity. These results suggest a concerted mechanism for the recruitment and activation of IRF-3 that can be subverted by viral proteins to evade innate immune responses.

PubMed: 27302953
DOI: 10.1073/pnas.1603269113

実験手法

X-RAY DIFFRACTION (2.5 Å)