View source for 4emt


==Crystal Structure of human STING bound to c-di-GMP==
<StructureSection load='4emt' size='340' side='right' caption='[[4emt]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4emt]] 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=4EMT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EMT FirstGlance]. <br>
</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>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4emu|4emu]]</td></tr>
<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>
<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=4emt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4emt OCA], [http://pdbe.org/4emt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4emt RCSB], [http://www.ebi.ac.uk/pdbsum/4emt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4emt ProSAT]</span></td></tr>
</table>
== Function ==
[[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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
STING (stimulator of interferon genes) is an innate immune sensor of cyclic dinucleotides that regulates the induction of type I interferons. STING's C-terminal domain forms a V-shaped dimer and binds a cyclic diguanylate monophosphate (c-di-GMP) at the dimer interface by both direct and solvent-mediated hydrogen bonds. Guanines of c-di-GMP stack against the phenolic rings of a conserved tyrosine, and mutations at the c-di-GMP binding surface reduce nucleotide binding and affect signaling.

Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system.,Shu C, Yi G, Watts T, Kao CC, Li P Nat Struct Mol Biol. 2012 Jun 24;19(7):722-4. doi: 10.1038/nsmb.2331. PMID:22728658<ref>PMID:22728658</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4emt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Stimulator of interferon genes|Stimulator of interferon genes]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Li, P]]
[[Category: Alpha/beta fold]]
[[Category: C-di-amp]]
[[Category: C-di-gmp]]
[[Category: Innate immune sensor]]
[[Category: Membrane protein]]