6dnk

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'''Unreleased structure'''
 
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The entry 6dnk is ON HOLD until Jun 06 2020
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==Human Stimulator of Interferon Genes==
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<StructureSection load='6dnk' size='340' side='right'caption='[[6dnk]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6dnk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DNK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DNK FirstGlance]. <br>
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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]] 1.95&#8491;</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=1SY:CGAMP'>1SY</scene></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=6dnk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dnk OCA], [https://pdbe.org/6dnk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dnk RCSB], [https://www.ebi.ac.uk/pdbsum/6dnk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dnk ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/STING_HUMAN STING_HUMAN] 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:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:21074459</ref> <ref>PMID:21947006</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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How the central innate immune protein, STING, is activated by its ligands remains unknown. Here, using structural biology and biochemistry, we report that the metazoan second messenger 2'3'-cGAMP induces closing of the human STING homodimer and release of the STING C-terminal tail, which exposes a polymerization interface on the STING dimer and leads to the formation of disulfide-linked polymers via cysteine residue 148. Disease-causing hyperactive STING mutations either flank C148 and depend on disulfide formation or reside in the C-terminal tail binding site and cause constitutive C-terminal tail release and polymerization. Finally, bacterial cyclic-di-GMP induces an alternative active STING conformation, activates STING in a cooperative manner, and acts as a partial antagonist of 2'3'-cGAMP signaling. Our insights explain the tight control of STING signaling given varying background activation signals and provide a therapeutic hypothesis for autoimmune syndrome treatment.
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Authors: Fernandez, D., Li, L., Ergun, S.L.
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STING Polymer Structure Reveals Mechanisms for Activation, Hyperactivation, and Inhibition.,Ergun SL, Fernandez D, Weiss TM, Li L Cell. 2019 Jun 12. pii: S0092-8674(19)30564-1. doi: 10.1016/j.cell.2019.05.036. PMID:31230712<ref>PMID:31230712</ref>
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Description: Human Stimulator of Interferon Genes
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Li, L]]
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<div class="pdbe-citations 6dnk" style="background-color:#fffaf0;"></div>
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[[Category: Fernandez, D]]
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[[Category: Ergun, S.L]]
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==See Also==
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*[[Stimulator of interferon genes protein|Stimulator of interferon genes protein]]
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*[[Stimulator of interferon genes protein 3D structures|Stimulator of interferon genes protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Ergun SL]]
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[[Category: Fernandez D]]
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[[Category: Li L]]

Current revision

Human Stimulator of Interferon Genes

PDB ID 6dnk

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