6nt8: Difference between revisions

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<SX load='6nt8' size='340' side='right' viewer='molstar' caption='[[6nt8]], [[Resolution|resolution]] 6.50&Aring;' scene=''>
<SX load='6nt8' size='340' side='right' viewer='molstar' caption='[[6nt8]], [[Resolution|resolution]] 6.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6nt8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NT8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NT8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6nt8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NT8 FirstGlance]. <br>
</td></tr><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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.5&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TMEM173 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>
<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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6nt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nt8 OCA], [http://pdbe.org/6nt8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nt8 RCSB], [http://www.ebi.ac.uk/pdbsum/6nt8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nt8 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nt8 OCA], [https://pdbe.org/6nt8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nt8 RCSB], [https://www.ebi.ac.uk/pdbsum/6nt8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nt8 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/STING_CHICK STING_CHICK] 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) (By similarity). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (By similarity). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:30842659). Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes and 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 (PubMed:30842659). In addition to promote the production of type I interferons, plays a direct role in autophagy (By similarity). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By similarity). The ERGIC serves as the membrane source for LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (By similarity). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (By similarity). Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (By similarity).[UniProtKB:Q86WV6]<ref>PMID:30842659</ref>  
Infections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds to and activates stimulator of interferon genes (STING; also known as TMEM173, MITA, ERIS and MPYS)(1-8). STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain(9-13). The cytoplasmic domain of STING forms a dimer, which undergoes a conformational change upon binding to cGAMP(9,14). However, it remains unclear how this conformational change leads to STING activation. Here we present cryo-electron microscopy structures of full-length STING from human and chicken in the inactive dimeric state (about 80 kDa in size), as well as cGAMP-bound chicken STING in both the dimeric and tetrameric states. The structures show that the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly. Closure of the ligand-binding domain, induced by cGAMP, leads to a 180 degrees rotation of the ligand-binding domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing. This model of STING oligomerization and activation is supported by our structure-based mutational analyses.
 
Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP.,Shang G, Zhang C, Chen ZJ, Bai XC, Zhang X Nature. 2019 Mar 6. pii: 10.1038/s41586-019-0998-5. doi:, 10.1038/s41586-019-0998-5. PMID:30842659<ref>PMID:30842659</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6nt8" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Stimulator of interferon genes|Stimulator of interferon genes]]
*[[Stimulator of interferon genes protein|Stimulator of interferon genes protein]]
*[[Stimulator of interferon genes protein 3D structures|Stimulator of interferon genes protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
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[[Category: Chick]]
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bai, X]]
[[Category: Bai X]]
[[Category: Chen, Z J]]
[[Category: Chen ZJ]]
[[Category: Shang, G]]
[[Category: Shang G]]
[[Category: Zhang, C]]
[[Category: Zhang C]]
[[Category: Zhang, X]]
[[Category: Zhang X]]
[[Category: Adaptor]]
[[Category: Er]]
[[Category: Immune system]]
[[Category: Membrane]]

Latest revision as of 12:22, 20 March 2024

Cryo-EM structure of full-length chicken STING in the cGAMP-bound tetrameric stateCryo-EM structure of full-length chicken STING in the cGAMP-bound tetrameric state

6nt8, resolution 6.50Å

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