Stimulator of interferon genes: Difference between revisions

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<StructureSection load='' size='350' side='right' caption='Structure of human STING CTD complex with c-GMP-AMP (PDB entry [[4loh]])' scene='57/573101/Cv/1'>
<StructureSection load='' size='350' side='right' caption='Structure of human STING CTD complex with c-GMP-AMP (PDB entry [[4loh]])' scene='57/573101/Cv/1'>
   
 
'''Stimulator of interferon genes''' (STING) induces production of type I interferon when cells are infected by viruses, mycobacteria and intracellular parasites.  STING recognizes and binds cyclic-di-GMP produced by bacteria and cyclic-GMP AMP (cGAMP) produced by viruses. The C-terminal domain (CTD) (residues 139-379 in human) of STING binds cyclic-di-GMP. STING is a facilitator of innate immune signaling<ref>PMID:26980676</ref>.
== Function ==
'''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>.
 
== Disease ==
STING mutations are associated with autoimmune diseases<ref>PMID:26235147</ref>.


== Structural highlights ==
== Structural highlights ==
The <scene name='57/573101/Cv/4'>cyclic dinucleotide binds the STING in a U-shaped cleft between the 2 monomers</scene><ref>PMID:23910378</ref>. Water molecules are shown as red spheres.
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>
==3D structures of stimulator of interferon genes protein==


==3D structures of STING==
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; PLPLRT/SD motif 342-379


*Stimulator of interferon genes
**[[6nt5]] – hSTING - human - Cryo EM<br />
 
**[[4ef5]], [[4f5w]], [[4f9e]] – hSTING C-di-GMP-binding domain<br />
Domain: CTD 139-379
**[[4f5e]], [[6mx0]] – hSTING C-di-GMP-binding domain (mutant)<br />
 
**[[6iyf]] – pSTING C-di-GMP-binding domain - pig<br />
**[[6nt5]] – hSTING – human - Cryo EM <br />
**[[4kc0]] – mSTING C-di-GMP-binding domain - mouse<br />
**[[4ef5]], [[4f5w]], [[4f9e]] – hSTING CTD<br />
**[[5gs5]] – rSTING C-di-GMP-binding domain - rat<br />
**[[4f5e]] – hSTING CTD (mutant)   <br />
**[[6nt6]] – cSTING - chicken - Cryo EM<br />
**[[4jc5]], [[4kc0]] – mSTING CTD - mouse <br />
**[[5cfo]], [[5cfr]] – aSTING – anemone<br />
**[[6nt6]] – cSTING – chicken – Cryo EM <br />
**[[5cfo]], [[5cfr]] – saSTING CTD – sea anemone <br />


*Stimulator of interferon genes complex with ligand
*Stimulator of interferon genes protein complex


**[[4ef4]], [[4f5y]], [[4f9g]], [[4emt]] – hSTING CTD + c-di-GMP <br />
**[[4ef4]], [[4emt]], [[4emu]], [[4f5y]], [[4f9g]], [[6rm0]], [[6s86]] – hSTING C-di-GMP-binding domain + GMP derivative<br />
**[[4f5d]] – hSTING CTD (mutant) + c-di-GMP <br />
**[[4f5d]] – hSTING C-di-GMP-binding domain (mutant) + GMP derivative <br />
**[[4ksy]] – hSTING CTD + c-GAMP <br />
**[[6cff]], [[6cy7]] – hSTING C-di-GMP-binding domain + AMP derivative <br />
**[[5bqx]] – hSTING CTD + c-GMP <br />
**[[4ksy]], [[4loh]], [[5bqx]], [[6dnk]], [[6xnp]], [[6s26]], [[6s27]] – hSTING C-di-GMP-binding domain + GMP-AMP derivative <br />
**[[4loh]], [[4loi]] – hSTING CTD + c-di-GMP derivative<br />
**[[4loi]], [[6mx3]], [[6mxe]] – hSTING C-di-GMP-binding domain (mutant) + GMP-AMP derivative <br />
**[[6cff]] – hSTING CTD + c-di-AMP <br />
**[[6dxg]], [[6dxl]], [[6ukm]], [[6uku]], [[6ukv]], [[6ukw]], [[6ukx]], [[6uky]], [[6ukz]], [[6ul0]] – hSTING C-di-GMP-binding domain + agonist <br />
**[[6dnk]] – hSTING CTD + c-GMP-AMP  <br />
**[[4qxo]] – hSTING C-di-GMP-binding domain + drug <br />
**[[4qxo]], [[4qxp]], [[4qxq]], [[4qxr]] – hSTING CTD + chemptherapeutic agent DMXAA<br />
**[[4qxp]], [[4qxq]], [[4qxr]] – hSTING C-di-GMP-binding domain (mutant) + drug <br />
**[[6dxl]], [[6dxg]] – hSTING CTD (mutant) + imidazole derivative  <br />
**[[5jej]] – hSTING PLPLRT/SD motif + IRF-3 CTD <br />
**[[6a06]] – pSTING CTD + c-GAMP - pig<br />
**[[6o8b]], [[6o8c]] – hSTING PLPLRT/SD motif (mutant) + TBK1 <br />
**[[6a05]] – pSTING CTD + purine derivative<br />
**[[6a03]], [[6a04]], [[6a05]], [[6a06]] – pSTING C-di-GMP-binding domain + ligand <br />
**[[6a04]] – pSTING CTD + c-di-GMP<br />
**[[4kby]] – mSTING C-di-GMP-binding domain+ GMP derivative<br />
**[[6a03]], [[6iyf]] – pSTING CTD + c-di-AMP<br />
**[[4loj]], [[4lok]], [[4yp1]] – mSTING C-di-GMP-binding domain + GMP-AMP derivative <br />
**[[5jej]] – hSTING residues 342-379 + IRF-3  <br />
**[[6xnn]] – mSTING C-di-GMP-binding domain + GMP-AMP derivative <br />
**[[4kby]] – mSTING CTD + c-di-GMP <br />
**[[4lol]] – mSTING C-di-GMP-binding domain + drug <br />
**[[4loj]], [[4lok]] – mSTING CTD + c-di-GMP derivative<br />
**[[4jc5]] – mSTING C-di-GMP-binding domain + immune activator <br />
**[[4yp1]] – mSTING CTD + c-di-AMP derivative<br />
**[[5grm]] – rSTING C-di-GMP-binding domain + GMP-AMP derivative <br />
**[[4lol]] – mSTING CTD + chemptherapeutic agent DMXAA<br />
**[[6nt7]], [[6nt8]] – cSTING + GMP-AMP derivative - Cryo EM<br />
**[[4kby]] – mSTING CTD + c-di-GMP <br />
**[[6nt9]] – cSTING + TBK1 - Cryo EM<br />
**[[6nt7]], [[6nt8]] – cSTING + GMP-AMP – Cryo EM <br />
**[[5cfl]], [[5cfm]], [[5cfq]] – aSTING C-di-GMP-binding domain + GMP derivative <br />
**[[6nt9]] – cSTING + TBK1 – Cryo EM <br />
**[[5cfp]] – aSTING C-di-GMP-binding domain (mutant) + GMP derivative<br />
**[[5cfl]] – saSTING CTD + c-di-GMP  <br />
**[[5cfn]] – aSTING C-di-GMP-binding domain + AMP derivative <br />
**[[5cfp]] – saSTING CTD (mutant) + c-di-GMP  <br />
**[[5cfq]] – saSTING CTD + c-AMP-GMP <br />
**[[5cfm]] – saSTING CTD + c-GMP <br />
**[[5cfn]] – saSTING CTD + c-di-AMP <br />


}}
}}

Revision as of 14:22, 29 January 2021


Function

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[1]. 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[2].

Disease

STING mutations are associated with autoimmune diseases[3].

Structural highlights

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 [4].


Structure of human STING CTD complex with c-GMP-AMP (PDB entry 4loh)

Drag the structure with the mouse to rotate

3D structures of stimulator of interferon genes protein3D structures of stimulator of interferon genes protein

Updated on 29-January-2021

ReferencesReferences

  1. ↑ Shang G, Zhang C, Chen ZJ, Bai XC, Zhang X. Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP. Nature. 2019 Mar 6. pii: 10.1038/s41586-019-0998-5. doi:, 10.1038/s41586-019-0998-5. PMID:30842659 doi:http://dx.doi.org/10.1038/s41586-019-0998-5
  2. ↑ Zhao B, Du F, Xu P, Shu C, Sankaran B, Bell SL, Liu M, Lei Y, Gao X, Fu X, Zhu F, Liu Y, Laganowsky A, Zheng X, Ji JY, West AP, Watson RO, Li P. A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1. Nature. 2019 May;569(7758):718-722. doi: 10.1038/s41586-019-1228-x. Epub 2019 May, 22. PMID:31118511 doi:http://dx.doi.org/10.1038/s41586-019-1228-x
  3. ↑ Dobbs N, Burnaevskiy N, Chen D, Gonugunta VK, Alto NM, Yan N. STING Activation by Translocation from the ER Is Associated with Infection and Autoinflammatory Disease. Cell Host Microbe. 2015 Aug 12;18(2):157-68. doi: 10.1016/j.chom.2015.07.001., Epub 2015 Jul 30. PMID:26235147 doi:http://dx.doi.org/10.1016/j.chom.2015.07.001
  4. ↑ Gao P, Ascano M, Zillinger T, Wang W, Dai P, Serganov AA, Gaffney BL, Shuman S, Jones RA, Deng L, Hartmann G, Barchet W, Tuschl T, Patel DJ. Structure-Function Analysis of STING Activation by c[G(2',5')pA(3',5')p] and Targeting by Antiviral DMXAA. Cell. 2013 Aug 15;154(4):748-62. doi: 10.1016/j.cell.2013.07.023. Epub 2013 Aug, 1. PMID:23910378 doi:10.1016/j.cell.2013.07.023

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman
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