Sandbox GGC12

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You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

Function

Controls the host immune response system against any pathogens through the recognition of molecular patterns tahat are specific to each microorganism. TLR3 is a nuclear-sensing TLR which is going to be essentially activated by a double-stranded RNA, which is a sign of a viral infection. Acts via the adapter TRIF/TICAM1, that leads to a NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response ^[3].

Disease

A rare complication of human herpesvirus 1 (HHV-1) infection, it occurs in only a small minority of HHV-1 infected individuals. There are characterized by a hemorrhagic necrosis of parts from both the temporal and frontal lobes. One of the onsets are that it invloves several days of fear, headache, seizures, stupor, and often coma, frequently with a fatal outcome ^[4].

Relevance

TRIF pathway

Various of the pathogens do target the signaling molecules and transcriptional regulators which are acting in the TRIF pathway, it goes on to demonstrate the main importance of this particular pathway which contributes to control of both viral and bacterial pathogens through a promotion of the inflammatory mediators and activators of antimicrobial responses. TRIF signaling also has both protective and pathologic roles in several chronic inflammatory disease conditions, as well as an essential function in wound‐repair processes ^[5].

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 ^[6].

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 ^{[7] [8]}.

Structural highlights

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. of Crystal Structure of Fab12. Here is a name='78/781196/Ser212/2'>Zoomed out view</scene> which is important