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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].
See also STING_Polymer_Structure_Reveals_Mechanisms_for_Activation,_Hyperactivation,_and_Inhibition_(Bi3323).
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. GMP-AMP binding site (water molecules are shown as red spheres). 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].
3D structures of stimulator of interferon genes protein
Stimulator of interferon genes protein 3D structures
- ↑ 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:https://dx.doi.org/10.1038/s41586-019-0998-5
- ↑ 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:https://dx.doi.org/10.1038/s41586-019-1228-x
- ↑ 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:https://dx.doi.org/10.1016/j.chom.2015.07.001
- ↑ 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
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