Sandbox GGC12: Difference between revisions
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TICAM1 | TICAM1 | ||
It is involved in an innate immunity against invading pathogens. The main adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate the NF-kappa-B and interferon-regulatory factor (IRF) activation, and they go on to induce apoptosis. Ligand binding for these receptors would result in TRIF recruitment through its TIR domain. It is a quite distinct protein-interaction motif which allows a recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, leads to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively. Phosphorylation by TBK1 on the pLxIS motif will lead to recruitments and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent immunity against invading pathogens. With the component of a multi-helicase-TICAM1 complex which will act as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and it plays a significant role in the activation of a cascade of antiviral responses including the induction of proinflammatory cytokines. Ubiquitously expressed but with higher levels in liver <ref>DOI 10.1016/j.jmb.2013.11.024</ref>. | |||
IRF3 | IRF3 | ||
Transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages. | Transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages <ref>DOI 10.1038/nri3581</ref> <ref>DOI 10.1016/j.coviro.2011.11.001</ref>. | ||
== Structural highlights == | == Structural highlights == | ||
Revision as of 23:07, 15 November 2020
Crystal Structure of Fab12
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