4loh

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{{STRUCTURE_4loh| PDB=4loh | SCENE= }}
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==Crystal structure of hSTING(H232) in complex with c[G(2',5')pA(3',5')p]==
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===Crystal structure of hSTING(H232) in complex with c[G(2',5')pA(3',5')p]===
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<StructureSection load='4loh' size='340' side='right' caption='[[4loh]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23910378}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4loh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LOH 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=1SY:CGAMP'>1SY</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4loi|4loi]], [[4loj|4loj]], [[4lok|4lok]], [[4lol|4lol]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TMEM173, ERIS, MITA, STING ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4loh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4loh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4loh RCSB], [http://www.ebi.ac.uk/pdbsum/4loh PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Binding of dsDNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) triggers formation of the metazoan second messenger c[G(2',5')pA(3',5')p], which binds the signaling protein STING with subsequent activation of the interferon (IFN) pathway. We show that human hSTING(H232) adopts a "closed" conformation upon binding c[G(2',5')pA(3',5')p] and its linkage isomer c[G(2',5')pA(2',5')p], as does mouse mSting(R231) on binding c[G(2',5')pA(3',5')p], c[G(3',5')pA(3',5')p] and the antiviral agent DMXAA, leading to similar "closed" conformations. Comparing hSTING to mSting, 2',5'-linkage-containing cGAMP isomers were more specific triggers of the IFN pathway compared to the all-3',5'-linkage isomer. Guided by structural information, we identified a unique point mutation (S162A) placed within the cyclic-dinucleotide-binding site of hSTING that rendered it sensitive to the otherwise mouse-specific drug DMXAA, a conclusion validated by binding studies. Our structural and functional analysis highlights the unexpected versatility of STING in the recognition of natural and synthetic ligands within a small-molecule pocket created by the dimerization of STING.
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==Function==
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Structure-Function Analysis of STING Activation by c[G(2',5')pA(3',5')p] and Targeting by Antiviral DMXAA.,Gao P, Ascano M, Zillinger T, Wang W, Dai P, Serganov AA, Gaffney BL, Shuman S, Jones RA, Deng L, Hartmann G, Barchet W, Tuschl T, Patel DJ Cell. 2013 Aug 15;154(4):748-62. doi: 10.1016/j.cell.2013.07.023. Epub 2013 Aug, 1. PMID:23910378<ref>PMID:23910378</ref>
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[[http://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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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4loh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LOH OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023910378</ref><references group="xtra"/><references/>
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*[[Stimulator of interferon genes|Stimulator of interferon genes]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Gao, P.]]
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[[Category: Gao, P]]
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[[Category: Patel, D J.]]
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[[Category: Patel, D J]]
[[Category: Immune system]]
[[Category: Immune system]]
[[Category: Innate immunity]]
[[Category: Innate immunity]]

Revision as of 15:34, 21 December 2014

Crystal structure of hSTING(H232) in complex with c[G(2',5')pA(3',5')p]

4loh, resolution 2.25Å

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