STING complex
Definition
Target type: cellularcomponent
A protein dimer containing two STING monomers. It binds cyclic purine di-nucleotides. Activation of the sting complex by 2',5'-3'-5'-cyclic GMP-AMP activates nuclear transcription factor kB (NF-kB) and interferon regulatory factor 3 (IRF3) which then induce transcription of the genes encoding type I IFN and cytokines active in the innate immune response. [GOC:bhm, PMID:22705373, PMID:23706668, PMID:23910378]
The STING (Stimulator of Interferon Genes) complex is a cytosolic protein complex that plays a crucial role in the innate immune response to cytosolic DNA. It is composed of several key components, including the STING protein itself, TBK1 (TANK-binding kinase 1), and IRF3 (Interferon Regulatory Factor 3). The STING complex assembles upon sensing cytosolic DNA, leading to the activation of TBK1 and the subsequent phosphorylation and nuclear translocation of IRF3. This ultimately results in the production of type I interferons, which are essential for antiviral immunity.
The cellular component of the STING complex can be described in the following manner:
- **STING (Stimulator of Interferon Genes):** A transmembrane protein located in the endoplasmic reticulum (ER) membrane. STING is a key component of the DNA sensing pathway. It contains a cytosolic N-terminal domain that binds to cyclic dinucleotides (CDNs), such as cGAMP, a second messenger produced by the enzyme cGAS upon DNA recognition. The C-terminal domain of STING is located in the ER lumen.
- **TBK1 (TANK-binding kinase 1):** A serine/threonine kinase that is recruited to the STING complex upon CDN binding. TBK1 is essential for the activation of IRF3.
- **IRF3 (Interferon Regulatory Factor 3):** A transcription factor that is phosphorylated by TBK1 and translocates to the nucleus, where it initiates the transcription of type I interferons.
In addition to these core components, other proteins may also be associated with the STING complex under specific conditions. These include:
- **TRAF proteins:** These proteins can interact with STING and contribute to the activation of downstream signaling pathways.
- **Ubiquitin ligases:** These enzymes can modify STING and influence its stability and activity.
- **Other adaptor proteins:** These proteins can facilitate the assembly of the STING complex and the recruitment of other signaling molecules.
The STING complex is a dynamic structure that can undergo significant changes in its composition and localization depending on the cellular context and the specific DNA stimulus. Understanding the cellular component of the STING complex is crucial for deciphering the intricate mechanisms of innate immune signaling in response to cytosolic DNA.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Stimulator of interferon genes protein | A transmembrane protein 173 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q86WV6] | Homo sapiens (human) |
Compounds (6)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| vadimezan | vadimezan : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by a 5,6-dimethyl-9-oxoxanthen-4-yl group. | monocarboxylic acid; xanthones | antineoplastic agent |
| mangostin | alpha-mangostin : A member of the class of xanthones that is 9H-xanthene substituted by hydroxy group at positions 1, 3 and 6, a methoxy group at position 7, an oxo group at position 9 and prenyl groups at positions 2 and 8. Isolated from the stems of Cratoxylum cochinchinense, it exhibits antioxidant, antimicrobial and antitumour activities. mangostin: xanthone from rind of Garcinia mangostana Linn. fruit | aromatic ether; phenols; xanthones | antimicrobial agent; antineoplastic agent; antioxidant; plant metabolite |
| cyclic diadenosine phosphate | cyclic di-AMP : A cyclic purine dinucleotide that is the 3',5'-cyclic dimer of AMP. | adenyl ribonucleotide; cyclic purine dinucleotide | Mycoplasma genitalium metabolite |
| bis(3',5')-cyclic diguanylic acid | cyclic purine dinucleotide; guanyl ribonucleotide | immunomodulator; signalling molecule | |
| cyclic guanosine monophosphate-adenosine monophosphate | c-GMP-AMP : A cyclic purine dinucleotide that consists of AMP and GMP units cyclised via 3',5'-linkages. | adenyl ribonucleotide; cyclic purine dinucleotide; guanyl ribonucleotide | |
| cyclic guanosine monophosphate-adenosine monophosphate | 2'-3'-cGAMP : A cyclic purine dinucleotide that consists of AMP and GMP units cyclised via 3',5'- and 2',5'-linkages respectively. | adenyl ribonucleotide; cyclic purine dinucleotide; guanyl ribonucleotide |