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5cfq

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Revision as of 12:03, 14 June 2023

Crystal structure of anemone STING (Nematostella vectensis) in complex with 2',3' cGAMP, c[G(2',5')pA(3',5')p]

Structural highlights

5cfq 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.
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]

Publication Abstract from PubMed

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 >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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5cfq"

@@ Line 3: / Line 3: @@
 <StructureSection load='5cfq' size='340' side='right'caption='[[5cfq]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5cfq]] 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=5CFQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CFQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5cfq]] 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=5CFQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CFQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1SY:CGAMP'>1SY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cfl|5cfl]], [[5cfm|5cfm]], [[5cfn|5cfn]], [[5cfo|5cfo]], [[5cfp|5cfp]], [[5cfr|5cfr]]</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=5cfq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cfq OCA], [https://pdbe.org/5cfq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cfq RCSB], [https://www.ebi.ac.uk/pdbsum/5cfq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cfq ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5cfq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cfq OCA], [http://pdbe.org/5cfq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cfq RCSB], [http://www.ebi.ac.uk/pdbsum/5cfq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cfq ProSAT]</span></td></tr>
 </table>
+== Function ==
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 20: @@
 ==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/>
@@ Line 26: / Line 27: @@
 </StructureSection>
 [[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]]

5cfq

From Proteopedia

Revision as of 12:03, 14 June 2023

Crystal structure of anemone STING (Nematostella vectensis) in complex with 2',3' cGAMP, c[G(2',5')pA(3',5')p]

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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