4jc5

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==Immune activator bound to receptor==
==Immune activator bound to receptor==
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<StructureSection load='4jc5' size='340' side='right' caption='[[4jc5]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
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<StructureSection load='4jc5' size='340' side='right'caption='[[4jc5]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4jc5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JC5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JC5 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4jc5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JC5 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1K5:(9-OXOACRIDIN-10(9H)-YL)ACETIC+ACID'>1K5</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tmem173, Eris Mita, Mpys, Sting ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1K5:(9-OXOACRIDIN-10(9H)-YL)ACETIC+ACID'>1K5</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jc5 OCA], [http://pdbe.org/4jc5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jc5 RCSB], [http://www.ebi.ac.uk/pdbsum/4jc5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jc5 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jc5 OCA], [https://pdbe.org/4jc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jc5 RCSB], [https://www.ebi.ac.uk/pdbsum/4jc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jc5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/STING_MOUSE STING_MOUSE]] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18559423</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:23258412</ref>
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[https://www.uniprot.org/uniprot/STING_MOUSE STING_MOUSE] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18559423</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:23258412</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Extensive research on antiviral small molecules starting in the early 1970s has led to the identification of 10-carboxymethyl-9-acridanone (CMA) as a potent type I interferon (IFN) inducer. Up to date, the mode of action of this antiviral molecule has remained elusive. Here we demonstrate that CMA mediates a cell-intrinsic type I IFN response, depending on the ER-resident protein STING. CMA directly binds to STING and triggers a strong antiviral response through the TBK1/IRF3 route. Interestingly, while CMA displays extraordinary activity in phosphorylating IRF3 in the murine system, CMA fails to activate human cells that are otherwise responsive to STING ligands. This failure to activate human STING can be ascribed to its inability to bind to the C-terminal ligand-binding domain of human STING. Crystallographic studies show that two CMA molecules bind to the central Cyclic diguanylate (c-diGMP)-binding pocket of the STING dimer and fold the lid region in a fashion similar, but partially distinct, to c-diGMP. Altogether, these results provide novel insight into ligand-sensing properties of STING and, furthermore, unravel unexpected species-specific differences of this innate sensor.
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Species-specific detection of the antiviral small-molecule compound CMA by STING.,Cavlar T, Deimling T, Ablasser A, Hopfner KP, Hornung V EMBO J. 2013 Apr 19. doi: 10.1038/emboj.2013.86. PMID:23604073<ref>PMID:23604073</ref>
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==See Also==
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*[[Stimulator of interferon genes protein|Stimulator of interferon genes protein]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[Stimulator of interferon genes protein 3D structures|Stimulator of interferon genes protein 3D structures]]
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</div>
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<div class="pdbe-citations 4jc5" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Lk3 transgenic mice]]
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[[Category: Large Structures]]
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[[Category: Deimling, T]]
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[[Category: Mus musculus]]
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[[Category: Hopfner, K P]]
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[[Category: Deimling T]]
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[[Category: Immune system]]
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[[Category: Hopfner KP]]
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[[Category: Innate immune receptor]]
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Current revision

Immune activator bound to receptor

PDB ID 4jc5

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