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4f9g

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{{STRUCTURE_4f9g| PDB=4f9g | SCENE= }}
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==Crystal structure of STING complex with Cyclic di-GMP.==
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===Crystal structure of STING complex with Cyclic di-GMP.===
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<StructureSection load='4f9g' size='340' side='right' caption='[[4f9g]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
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{{ABSTRACT_PUBMED_22705373}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4f9g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F9G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F9G 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=C2E:9,9-[(2R,3R,3AS,5S,7AR,9R,10R,10AS,12S,14AR)-3,5,10,12-TETRAHYDROXY-5,12-DIOXIDOOCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECINE-2,9-DIYL]BIS(2-AMINO-1,9-DIHYDRO-6H-PURIN-6-ONE)'>C2E</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f9e|4f9e]]</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 HUMAN])</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=4f9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f9g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f9g RCSB], [http://www.ebi.ac.uk/pdbsum/4f9g 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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Detection of foreign materials is the first step of successful immune responses. Stimulator of interferon genes (STING) was shown to directly bind cyclic diguanylate monophosphate (c-di-GMP), a bacterial second messenger, and to elicit strong interferon responses. Here we elucidate the structural features of the cytosolic c-di-GMP binding domain (CBD) of STING and its complex with c-di-GMP. The CBD exhibits an alpha + beta fold and is a dimer in the crystal and in solution. Surprisingly, one c-di-GMP molecule binds to the central crevice of a STING dimer, using a series of stacking and hydrogen bonding interactions. We show that STING is autoinhibited by an intramolecular interaction between the CBD and the C-terminal tail (CTT) and that c-di-GMP releases STING from this autoinhibition by displacing the CTT. The structures provide a remarkable example of pathogen-host interactions in which a unique microbial molecule directly engages the innate immune system.
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==Function==
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Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING.,Yin Q, Tian Y, Kabaleeswaran V, Jiang X, Tu D, Eck MJ, Chen ZJ, Wu H Mol Cell. 2012 Jun 29;46(6):735-45. Epub 2012 Jun 14. PMID:22705373<ref>PMID:22705373</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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[[4f9g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F9G OCA].
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</div>
==See Also==
==See Also==
*[[Stimulator of interferon genes|Stimulator of interferon genes]]
*[[Stimulator of interferon genes|Stimulator of interferon genes]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:022705373</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Human]]
[[Category: Human]]
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[[Category: Kabaleeswaran, V.]]
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[[Category: Kabaleeswaran, V]]
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[[Category: Wu, H.]]
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[[Category: Wu, H]]
[[Category: Immune system c-di-gmp dimerisation]]
[[Category: Immune system c-di-gmp dimerisation]]
[[Category: Interferon]]
[[Category: Interferon]]
[[Category: Protein binding]]
[[Category: Protein binding]]

Revision as of 17:04, 21 December 2014

Crystal structure of STING complex with Cyclic di-GMP.

4f9g, resolution 2.95Å

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