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Stimulator of interferon genes protein: Difference between revisions

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<StructureSection load='6uec' size='350' side='right' caption='UDP-3-O-(3-hydroxymyristoyl)glucosamine acyltransferase complex with Naphthalene derivative, DMSO and Mg+2 (PDB code [[6uec]])' scene='87/873780/Cv/3'>
<StructureSection load='4loh' size='350' side='right' caption='Human stimulator of interferon genes protein C-di-GMP-binding domain complex with GMP-AMP (PDB code [[4loh]])' scene=''>


== Function ==
== Function ==
'''Stimulator of interferon genes protein''' or '''transmembrane protein 173''' (STING) is involved in the third step of the biosynthesis of lipid A which is a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.  Thus, LpxD is essential to survival of Gram-negative bacteria.  It catalyzes the N-acylation of UDP-3-O-(3-hydroxytetradeanoyl)glucosamine<ref>PMID:18456814</ref>. LpxD is structurally similar to LpxA which functions as the first enzye in the lipid A biosynthesis.
'''Stimulator of interferon genes protein''' or '''transmembrane protein 173''' (STING) is an ER-associated membrane protein.  STING signals immune responses in human and other animals. STING is activated by cyclic GMP-AMP produced by [[Cyclic GMP-AMP synthase]] whose activity is triggered by infections of DNA-containing pathogens<ref>PMID:30842659</ref>. A PLPLRT/SD conserved motif at the STING C-terminal plays a critical role in turning on the immune system to fight against viral infections<ref>PMID:31118511</ref>.


== Relevance ==
== Disease ==
LpxD inhibitors are antimicrobials<ref>PMID:22530734</ref>.
STING mutations are associated with autoimmune diseases<ref>PMID:26235147</ref>.


== Structural highlights ==
== Structural highlights ==
The biological assembly of UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase is <scene name='87/873780/Cv/4'>homotrimer</scene> (PDB code [[6uec]]). The 3D structure of LpxD complex with a ligand shows the binding site to be situated at <scene name='87/873780/Cv/6'>the interface of the crystallographic dimer</scene>. There are extensive polar interactions with LpxD as well as hydrogen bonds<ref>PMID:31664082</ref>.
The 3D structure of the complex between human STING and cyclic GMP-AMP shows the dinucleotide bound by the symmetric dimer of STING.  The U-shaped cleft between the 2 subunits makes numerous interactions with the U-shaped ligand.  A Tyr residue from each monomer stacks against each of the purine moieties while an Arg residue from each monomer forms hydrogen bonds to the dinucleotide <ref>PMID:23910378</ref>.


</StructureSection>
</StructureSection>
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
{{#tree:id=OrganizedByTopic|openlevels=0|
*Stimulator of interferon genes protein; domains - C-di-GMP-binding 154-341
*Stimulator of interferon genes protein; domains - C-di-GMP-binding 154-341; PLPLRT/SD motif 342-379


**[[6nt5]] – hSTING - human - Cryo EM<br />
**[[6nt5]] – hSTING - human - Cryo EM<br />
**[[6mx0]] – hSTING C-di-GMP-binding domain (mutant)<br />
**[[4ef5]], [[4f5w]], [[4f9e]] – hSTING C-di-GMP-binding domain<br />
**[[4f5e]], [[6mx0]] – hSTING C-di-GMP-binding domain (mutant)<br />
**[[6iyf]] – pSTING C-di-GMP-binding domain - pig<br />
**[[6iyf]] – pSTING C-di-GMP-binding domain - pig<br />
**[[4kc0]] – mSTING C-di-GMP-binding domain - mouse<br />
**[[4kc0]] – mSTING C-di-GMP-binding domain - mouse<br />
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*Stimulator of interferon genes protein complex
*Stimulator of interferon genes protein complex


**[[4emt]], [[4emu]], [[6rm0]], [[6s86]] – hSTING C-di-GMP-binding domain + GMP derivative<br />
**[[4ef4]], [[4emt]], [[4emu]], [[4f5y]], [[4f9g]], [[6s86]] – hSTING C-di-GMP-binding domain + GMP derivative<br />
**[[6cff]] – hSTING C-di-GMP-binding domain + AMP derivative <br />
**[[4f5d]] – hSTING C-di-GMP-binding domain (mutant) + GMP derivative <br />
**[[4ksy]], [[4loh]], [[5bqx]], [[6dnk]], [[6s26]], [[6s27]] – hSTING C-di-GMP-binding domain + GMP-AMP derivative <br />
**[[6cff]], [[6cy7]] – hSTING C-di-GMP-binding domain + AMP derivative <br />
**[[4ksy]], [[4loh]], [[5bqx]], [[6dnk]], [[6xnp]], [[6s26]], [[6s27]] – hSTING C-di-GMP-binding domain + GMP-AMP derivative <br />
**[[4loi]], [[6mx3]], [[6mxe]] – hSTING C-di-GMP-binding domain (mutant) + GMP-AMP derivative <br />
**[[4loi]], [[6mx3]], [[6mxe]] – hSTING C-di-GMP-binding domain (mutant) + GMP-AMP derivative <br />
**[[6dxg]], [[6dxl]], [[6ukm]], [[6uku]], [[6ukv]], [[6ukw]], [[6ukx]], [[6uky]], [[6ukz]], [[6ul0]] – hSTING C-di-GMP-binding domain + agonist <br />
**[[6dxg]], [[6dxl]], [[6ukm]], [[6uku]], [[6ukv]], [[6ukw]], [[6ukx]], [[6uky]], [[6ukz]], [[6ul0]] – hSTING C-di-GMP-binding domain + agonist <br />
**[[4qxo]] – hSTING C-di-GMP-binding domain + drug <br />
**[[4qxo]] – hSTING C-di-GMP-binding domain + drug <br />
**[[4qxp]], [[4qxq]], [[4qxr]] – hSTING C-di-GMP-binding domain (mutant) + drug <br />
**[[4qxp]], [[4qxq]], [[4qxr]] – hSTING C-di-GMP-binding domain (mutant) + drug <br />
**[[5jej]] – hSTING PLPLRT/SD motif + IRF-3 CTD <br />
**[[6o8b]], [[6o8c]] – hSTING PLPLRT/SD motif (mutant) + TBK1 <br />
**[[6a03]], [[6a04]], [[6a05]], [[6a06]] – pSTING C-di-GMP-binding domain + ligand <br />
**[[6a03]], [[6a04]], [[6a05]], [[6a06]] – pSTING C-di-GMP-binding domain + ligand <br />
**[[4kby]] – mSTING C-di-GMP-binding domain+ GMP derivative<br />
**[[4kby]] – mSTING C-di-GMP-binding domain+ GMP derivative<br />

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Michal Harel, Joel L. Sussman
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