5cfl: Difference between revisions

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<StructureSection load='5cfl' size='340' side='right'caption='[[5cfl]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
<StructureSection load='5cfl' size='340' side='right'caption='[[5cfl]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5cfl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Nemve Nemve]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CFL FirstGlance]. <br>
<table><tr><td colspan='2'>[[5cfl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nematostella_vectensis Nematostella vectensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CFL 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=FLC:CITRATE+ANION'>FLC</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.836&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cfm|5cfm]], [[5cfn|5cfn]], [[5cfo|5cfo]], [[5cfp|5cfp]], [[5cfq|5cfq]], [[5cfr|5cfr]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=FLC:CITRATE+ANION'>FLC</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">v1g246111 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=45351 NEMVE])</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=5cfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cfl OCA], [https://pdbe.org/5cfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cfl RCSB], [https://www.ebi.ac.uk/pdbsum/5cfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cfl ProSAT]</span></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=5cfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cfl OCA], [http://pdbe.org/5cfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cfl RCSB], [http://www.ebi.ac.uk/pdbsum/5cfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cfl ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/STING_NEMVE STING_NEMVE] Sensor of cytosolic DNA from bacteria and viruses that promotes autophagy (PubMed:30842662). Acts by recognizing and binding cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA in the cytosol (PubMed:26300263, PubMed:30842662). Following cGAMP-binding, promotes the formation of autophagosomes, leading to target cytosolic DNA for degradation by the lysosome (PubMed:30842662). Exhibits guanine base-specific ligand recognition. Binds 3'-3'linked cGAMP, 2'-3' linked cGAMP and 3'-3' linked c-di-GMP with much greater affinity as compared to 3'-3' linked c-di-AMP (PubMed:26300263). Lacks the C-terminal tail (CTT) found in mammalian orthologs which is essential for interferon signaling (PubMed:26300263).<ref>PMID:26300263</ref> <ref>PMID:30842662</ref>  
In humans, the cGAS-STING immunity pathway signals in response to cytosolic DNA via 2',3' cGAMP, a cyclic dinucleotide (CDN) second messenger containing mixed 2'-5' and 3'-5' phosphodiester bonds. Prokaryotes also produce CDNs, but these are exclusively 3' linked, and thus the evolutionary origins of human 2',3' cGAMP signaling are unknown. Here we illuminate the ancient origins of human cGAMP signaling by discovery of a functional cGAS-STING pathway in Nematostella vectensis, an anemone species &gt;500 million years diverged from humans. Anemone cGAS appears to produce a 3',3' CDN that anemone STING recognizes through nucleobase-specific contacts not observed in human STING. Nevertheless, anemone STING binds mixed-linkage 2',3' cGAMP indistinguishably from human STING, trapping a unique structural conformation not induced by 3',3' CDNs. These results reveal that human mixed-linkage cGAMP achieves universal signaling by exploiting a deeply conserved STING conformational intermediate, providing critical insight for therapeutic targeting of the STING pathway.
 
Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling.,Kranzusch PJ, Wilson SC, Lee AS, Berger JM, Doudna JA, Vance RE Mol Cell. 2015 Aug 19. pii: S1097-2765(15)00580-8. doi:, 10.1016/j.molcel.2015.07.022. PMID:26300263<ref>PMID:26300263</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5cfl" 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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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Nemve]]
[[Category: Nematostella vectensis]]
[[Category: Berger, J M]]
[[Category: Berger JM]]
[[Category: Doudna, J A]]
[[Category: Doudna JA]]
[[Category: Kranzusch, P J]]
[[Category: Kranzusch PJ]]
[[Category: Lee, A S.Y]]
[[Category: Lee ASY]]
[[Category: Vance, R E]]
[[Category: Vance RE]]
[[Category: Wilson, S C]]
[[Category: Wilson SC]]
[[Category: Cyclic-dinucleotide binding domain]]
[[Category: Immune system]]
[[Category: Sting]]

Latest revision as of 15:20, 6 March 2024

Crystal structure of anemone STING (Nematostella vectensis) in complex with 3', 3' c-di-GMP, c[G(3', 5')pG(3', 5')p]Crystal structure of anemone STING (Nematostella vectensis) in complex with 3', 3' c-di-GMP, c[G(3', 5')pG(3', 5')p]

Structural highlights

5cfl is a 2 chain structure with sequence from Nematostella vectensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.836Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

STING_NEMVE Sensor of cytosolic DNA from bacteria and viruses that promotes autophagy (PubMed:30842662). Acts by recognizing and binding cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA in the cytosol (PubMed:26300263, PubMed:30842662). Following cGAMP-binding, promotes the formation of autophagosomes, leading to target cytosolic DNA for degradation by the lysosome (PubMed:30842662). Exhibits guanine base-specific ligand recognition. Binds 3'-3'linked cGAMP, 2'-3' linked cGAMP and 3'-3' linked c-di-GMP with much greater affinity as compared to 3'-3' linked c-di-AMP (PubMed:26300263). Lacks the C-terminal tail (CTT) found in mammalian orthologs which is essential for interferon signaling (PubMed:26300263).[1] [2]

See Also

References

  1. ↑ Kranzusch PJ, Wilson SC, Lee AS, Berger JM, Doudna JA, Vance RE. Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling. Mol Cell. 2015 Aug 19. pii: S1097-2765(15)00580-8. doi:, 10.1016/j.molcel.2015.07.022. PMID:26300263 doi:http://dx.doi.org/10.1016/j.molcel.2015.07.022
  2. ↑ Gui X, Yang H, Li T, Tan X, Shi P, Li M, Du F, Chen ZJ. Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature. 2019 Mar;567(7747):262-266. PMID:30842662 doi:10.1038/s41586-019-1006-9

5cfl, resolution 1.84Å

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