Cyclic di-AMP

Last updated
Cyclic di-AMP
Cyclic di-adenosine monophosphate.svg
Names
IUPAC name
(1S,6R,8R,9R,10S,15R,17R,18R)-8,17-Bis(6-aminopurin-9-yl)-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3λ5,12λ5-diphosphatricyclo[13.3.0.06,10]octadecane-9,18-diol
Other names
3',5'-cyclic di-AMP; c-di-AMP; c-di-adenosine monophosphate
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
PubChem CID
UNII
  • InChI=1S/C20H24N10O12P2/c21-15-9-17(25-3-23-15)29(5-27-9)19-11(31)13-7(39-19)1-37-43(33,34)42-14-8(2-38-44(35,36)41-13)40-20(12(14)32)30-6-28-10-16(22)24-4-26-18(10)30/h3-8,11-14,19-20,31-32H,1-2H2,(H,33,34)(H,35,36)(H2,21,23,25)(H2,22,24,26)/t7-,8-,11-,12-,13-,14-,19-,20-/m1/s1
    Key: PDXMFTWFFKBFIN-XPWFQUROSA-N
  • C1[C@@H]2[C@H]([C@H]([C@@H](O2)N3C=NC4=C(N=CN=C43)N)O)OP(=O)(OC[C@@H]5[C@H]([C@H]([C@@H](O5)N6C=NC7=C(N=CN=C76)N)O)OP(=O)(O1)O)O
Properties
C20H24N10O12P2
Molar mass 658.418 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Cyclic di-AMP (also called c-di-AMP and c-di-adenosine monophosphate) is a second messenger used in signal transduction in bacteria and archaea. [1] [2] [3] It is present in many Gram-positive bacteria, some Gram-negative species, and archaea of the phylum euryarchaeota. [2] [3]

Contents

Cyclic di-AMP crystal structure Cyclic di-AMP imaged using PyMOL.png
Cyclic di-AMP crystal structure

It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine pentaphosphate ((p)ppGpp), and cyclic di-GMP (c-di-GMP). c-di-AMP is a signaling nucleotide used in signaling pathways that trigger outputs by using receptor or target proteins to sense c-di-AMP concentrations in the cell.

In bacteria, cyclic di-AMP has been implicated in the control of growth, cell wall homeostasis, bacterial biofilm formation and virulence gene expression, heat and osmotic stress regulation and responses, sporulation, potassium transport, lysis, and antibiotic resistance. [2] [4]

In humans, cyclic di-AMP has been implicated in the control of innate immune response and antiviral response against pathogens. The dinucleotide is also produced by numerous human pathogens, prompting the exploration of numerous c-di-AMP-regulating pathways both in humans and in bacteria.

Synthesis

Cyclic di-AMP is synthesized by a membrane-bound diadenylate cyclase (also called diadenylyl cyclase, CdA, and DAC) enzyme called CdaA (DacA). DacA condenses two ATP molecules to make c-di-AMP, releasing 2 pyrophosphates in the process. [5] [6] DacA requires a manganese or cobalt metal ion cofactor. [7] Most bacteria possess only one DAC enzyme, but some bacteria like B. subtilis possess two additional DAC enzymes (DisA and CdaS). [2]

Cyclic di-AMP synthesis is inhibited by the GImM I154F mutation in the Lactococcus lactis bacterium. GImM is the phosphoglucosamine mutase enzyme that interconverts glucosamine-6-phosphate to glucosamine-1-phosphate to later form cell wall peptidoglycan and other polymers. [4] The I154F mutation inhibits CdA activity by binding to it more strongly than wild-type GImM binds. [4] Thus, GImM modulates c-di-AMP levels.

Synthesis is regulated a number of ways, including negative feedback inhibition and upregulation through a decrease in phosphodiesterase. [2]

c-di-AMP synthesis and degradation reaction C-di-AMP synthesis and degradation reaction.png
c-di-AMP synthesis and degradation reaction

Degradation

Phosphodiesterase (PDE) enzymes degrade cyclic di-AMP to the linear molecule 5’-pApA (phosphadenylyl adenosine). 5'-pApA is also involved in a feedback inhibition loop that limits GdpP gene-dependent c-di-AMP hydrolysis, leading to elevated c-di-AMP levels. [8]

Regulation

Since cyclic di-AMP is a signaling nucleotide, it is presumed to adhere to the same regulation pathways, where environmental changes are sensed by synthesis or degradation enzymes, which modulate enzyme concentration. Regulation of c-di-AMP is critical because high c-di-AMP levels lead to abnormal physiology, growth defects, and reduced virulence in infection. [9] In some bacteria, loss of the phosphodiesterases that degrade c-di-AMP leads to cell death. [9] [10] [11]

It is possible that in addition to enzymatic regulation, intracellular c-di-AMP levels can be regulated by active transport via multidrug resistance transporters that secrete c-di-AMP from the cytoplasm. Listeria monocytogenes has demonstrated such an effect. [9]

At high concentrations, cyclic di-AMP binds to receptor and target proteins to control specific pathways. Elevated c-di-AMP levels have also been linked to increased resistance toward cell wall-damaging antibiotics (e.g. β-lactams) and reduced cellular turgor. [12] [13]

Fatty acid synthesis

Cyclic di-AMP has been linked to fatty acid synthesis regulation in Mycobacterium smegmatis , the growth of S. aureus in conditions of low potassium, the sensing of DNA integrity in B. subtilis , and cell wall homeostasis in multiple species. [14] [15] [16] [17]

Cell wall precursor, and thus peptidoglycan precursor, biosynthesis activity can also affect c-di-AMP levels in the cell. [4] Similarly, c-di-AMP levels affect peptidoglycan precursor synthesis, suggesting a strong link between the c-di-AMP and peptidoglycan synthetic pathways. [17]

Cell lysis and RNA synthesis

It is suggested that cyclic di-AMP is involved in the regulation of cell lysis. Studies have shown that bacterial mutant strains with low c-di-AMP levels lysed significantly faster than their parent strains. [4] [18]

Cyclic di-AMP has also been linked to bacterial RNA synthesis inhibition. c-di-AMP stimulates the production of (p)ppGpp, an alarmone involved in bacterial stringent response. [19]

STING pathway

In eukaryotic cells, c-di-AMP is sensed and subsequently elicits a type I interferon (IFN) response, leading to the activation of defense mechanisms against viral infection. This detection and activation pathway involves STING, TBK1, and IRF3. [20] [21] c-di-AMP may also stimulate dendritic cells, leading to T cell activation. [22]

c-di-AMP activates the innate immune pathway STING (stimulator of interferon genes) to detect damaged DNA. The nucleotide either binds to the helicase DDX41, which in turn activates the STING pathway, or directly binds to the STING protein. [23] Cyclic di-AMP has been identified (along with 2’3’-cGAMP) as a ligand that induces closing of the STING dimer, leading to STING polymerization and pathway activation. [24] When a type I IFN response is not induced in response to c-di-AMP, STING is unable to relocate from the endoplasmic reticulum to the cytoplasm for pathway activation, suggesting that c-di-AMP is a predominant ligand in STING polymerization, and thus activation, via intracellular translocation. [24] [25]

See also

Related Research Articles

<span class="mw-page-title-main">Adenylyl cyclase</span> Enzyme with key regulatory roles in most cells

Adenylate cyclase is an enzyme with systematic name ATP diphosphate-lyase . It catalyzes the following reaction:

<span class="mw-page-title-main">Cyclic adenosine monophosphate</span> Cellular second messenger

Cyclic adenosine monophosphate is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway.

<span class="mw-page-title-main">Adenosine monophosphate</span> Chemical compound

Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine. It is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it takes the form of the prefix adenylyl-.

<span class="mw-page-title-main">Cyclic nucleotide</span> Cyclic nucleic acid

A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, and a single phosphate group. As can be seen in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) images, the 'cyclic' portion consists of two bonds between the phosphate group and the 3' and 5' hydroxyl groups of the sugar, very often a ribose.

<span class="mw-page-title-main">Phosphodiesterase</span> Class of enzymes

A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases.

<span class="mw-page-title-main">Cyclic guanosine monophosphate</span> Chemical compound

Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface. Through protein kinases activation, cGMP can relax smooth muscle. cGMP concentration in urine can be measured for kidney function and diabetes detection.

<span class="mw-page-title-main">Guanylate cyclase</span> Lyase enzyme that synthesizes cGMP from GTP

Guanylate cyclase is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate:

<span class="mw-page-title-main">Cyclic nucleotide–gated ion channel</span> Family of transport proteins

Cyclic nucleotide–gated ion channels or CNG channels are ion channels that function in response to the binding of cyclic nucleotides. CNG channels are nonselective cation channels that are found in the membranes of various tissue and cell types, and are significant in sensory transduction as well as cellular development. Their function can be the result of a combination of the binding of cyclic nucleotides and either a depolarization or a hyperpolarization event. Initially discovered in the cells that make up the retina of the eye, CNG channels have been found in many different cell types across both the animal and the plant kingdoms. CNG channels have a very complex structure with various subunits and domains that play a critical role in their function. CNG channels are significant in the function of various sensory pathways including vision and olfaction, as well as in other key cellular functions such as hormone release and chemotaxis. CNG channels have also been found to exist in prokaryotes, including many spirochaeta, though their precise role in bacterial physiology remains unknown.

cGMP-specific phosphodiesterase type 5 Mammalian protein found in Homo sapiens

Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system.

<span class="mw-page-title-main">Cyclic nucleotide phosphodiesterase</span> Class of enzymes

3′,5′-cyclic-nucleotide phosphodiesterases (EC 3.1.4.17) are a family of phosphodiesterases. Generally, these enzymes hydrolyze a nucleoside 3′,5′-cyclic phosphate to a nucleoside 5′-phosphate:

<span class="mw-page-title-main">Phosphodiesterase 3</span> Class of enzymes

PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism. Most of the PDE families are composed of more than one gene. PDE3 is clinically significant because of its role in regulating heart muscle, vascular smooth muscle and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals, but their use is limited by arrhythmic effects and they can increase mortality in some applications.

Phosphodiesterase 1, PDE1, EC 3.1.4.1, systematic name oligonucleotide 5′-nucleotidohydrolase) is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase. It is one of the 11 families of phosphodiesterase (PDE1-PDE11). Phosphodiesterase 1 has three subtypes, PDE1A, PDE1B and PDE1C which divide further into various isoforms. The various isoforms exhibit different affinities for cAMP and cGMP.

<span class="mw-page-title-main">Phosphodiesterase 2</span> Class of enzymes

The PDE2 enzyme is one of 21 different phosphodiesterases (PDE) found in mammals. These different PDEs can be subdivided to 11 families. The different PDEs of the same family are functionally related despite the fact that their amino acid sequences show considerable divergence. The PDEs have different substrate specificities. Some are cAMP selective hydrolases, others are cGMP selective hydrolases and the rest can hydrolyse both cAMP and cGMP.

<span class="mw-page-title-main">PDE7A</span> Protein-coding gene in the species Homo sapiens

High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A is an enzyme that in humans is encoded by the PDE7A gene. Mammals possess 21 cyclic nucleotide phosphodiesterase (PDE) genes that are pharmacologically grouped into 11 families. PDE7A is one of two genes in the PDE7 family, the other being PDE7B. The PDE7 family, along with the PDE4 and PDE8 families, are cAMP-specific, showing little to no activity against 3', 5'-cyclic guanosine monophosphate (cGMP).

In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication.

<span class="mw-page-title-main">Cyclic di-GMP</span> Chemical compound

Cyclic di-GMP is a second messenger used in signal transduction in a wide variety of bacteria. Cyclic di-GMP is not known to be used by archaea, and has only been observed in eukaryotes in Dictyostelium. The biological role of cyclic di-GMP was first uncovered when it was identified as an allosteric activator of a cellulose synthase found in Gluconacetobacter xylinus in order to produce microbial cellulose.

<span class="mw-page-title-main">Diguanylate cyclase</span>

In enzymology, diguanylate cyclase, also known as diguanylate kinase, is an enzyme that catalyzes the chemical reaction:

<span class="mw-page-title-main">Cyclic guanosine monophosphate–adenosine monophosphate</span> Chemical compound

Cyclic guanosine monophosphate–adenosine monophosphate is the first cyclic di-nucleotide found in metazoa. In mammalian cells, cGAMP is synthesized by cyclic GMP-AMP synthase (cGAS) from ATP and GTP upon cytosolic DNA stimulation. cGAMP produced by cGAS contains mixed phosphodiester linkages, with one between 2'-OH of GMP and 5'-phosphate of AMP and the other between 3'-OH of AMP and 5'-phosphate of GMP.

<span class="mw-page-title-main">Stimulator of interferon genes</span> Protein-coding gene in the species Homo sapiens

Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a protein that in humans is encoded by the STING1 gene.

The cGAS–STING pathway is a component of the innate immune system that functions to detect the presence of cytosolic DNA and, in response, trigger expression of inflammatory genes that can lead to senescence or to the activation of defense mechanisms. DNA is normally found in the nucleus of the cell. Localization of DNA to the cytosol is associated with tumorigenesis, viral infection, and invasion by some intracellular bacteria. The cGAS – STING pathway acts to detect cytosolic DNA and induce an immune response.

References

  1. ↑ Dey B, Dey RJ, Cheung LS, Pokkali S, Guo H, Lee JH, Bishai WR (April 2015). "A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis". Nature Medicine. 21 (4): 401–6. doi:10.1038/nm.3813. PMC   4390473 . PMID   25730264.
  2. 1 2 3 4 5 Corrigan RM, Gründling A (August 2013). "Cyclic di-AMP: another second messenger enters the fray". Nature Reviews. Microbiology. 11 (8): 513–24. doi:10.1038/nrmicro3069. hdl: 10044/1/19649 . PMID   23812326. S2CID   29830881.
  3. 1 2 Braun F, Thomalla L, van der Does C, Quax TE, Allers T, Kaever V, Albers SV (September 2019). "Cyclic nucleotides in archaea: Cyclic di-AMP in the archaeon Haloferax volcanii and its putative role". MicrobiologyOpen. 8 (9): e00829. doi: 10.1002/mbo3.829 . PMC   6741144 . PMID   30884174.
  4. 1 2 3 4 5 Zhu Y, Pham TH, Nhiep TH, Vu NM, Marcellin E, Chakrabortti A, et al. (March 2016). "Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in Lactococcus lactis". Molecular Microbiology. 99 (6): 1015–27. doi:10.1111/mmi.13281. hdl: 10453/41116 . PMID   26585449. S2CID   24427957.
  5. ↑ Pham TH, Liang ZX, Marcellin E, Turner MS (November 2016). "Replenishing the cyclic-di-AMP pool: regulation of diadenylate cyclase activity in bacteria". Current Genetics. 62 (4): 731–738. doi:10.1007/s00294-016-0600-8. PMID   27074767. S2CID   1563228.
  6. ↑ Commichau FM, Heidemann JL, Ficner R, Stülke J (January 2019). Margolin W (ed.). "Making and Breaking of an Essential Poison: the Cyclases and Phosphodiesterases That Produce and Degrade the Essential Second Messenger Cyclic di-AMP in Bacteria". Journal of Bacteriology. 201 (1): e00462–18, /jb/201/1/JB.00462–18.atom. doi:10.1128/JB.00462-18. PMC   6287462 . PMID   30224435.
  7. ↑ Rosenberg J, Dickmanns A, Neumann P, Gunka K, Arens J, Kaever V, et al. (March 2015). "Structural and biochemical analysis of the essential diadenylate cyclase CdaA from Listeria monocytogenes". The Journal of Biological Chemistry. 290 (10): 6596–606. doi: 10.1074/jbc.M114.630418 . PMC   4358292 . PMID   25605729.
  8. ↑ Bowman L, Zeden MS, Schuster CF, Kaever V, Gründling A (December 2016). "New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus". The Journal of Biological Chemistry. 291 (53): 26970–26986. doi: 10.1074/jbc.M116.747709 . PMC   5207132 . PMID   27834680.
  9. 1 2 3 Huynh TN, Woodward JJ (April 2016). "Too much of a good thing: regulated depletion of c-di-AMP in the bacterial cytoplasm". Current Opinion in Microbiology. Cell regulation. 30: 22–29. doi:10.1016/j.mib.2015.12.007. PMC   4821758 . PMID   26773214.
  10. ↑ Gundlach J, Mehne FM, Herzberg C, Kampf J, Valerius O, Kaever V, Stülke J (October 2015). O'Toole GA (ed.). "An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis". Journal of Bacteriology. 197 (20): 3265–74. doi:10.1128/JB.00564-15. PMC   4573722 . PMID   26240071.
  11. ↑ Blötz C, Treffon K, Kaever V, Schwede F, Hammer E, Stülke J (2017-07-13). "Mycoplasma pneumoniae". Frontiers in Microbiology. 8: 1328. doi: 10.3389/fmicb.2017.01328 . PMC   5508000 . PMID   28751888.
  12. ↑ Wang X, Davlieva M, Reyes J, Panesso D, Arias CA, Shamoo Y (March 2017). "A Novel Phosphodiesterase of the GdpP Family Modulates Cyclic di-AMP Levels in Response to Cell Membrane Stress in Daptomycin-Resistant Enterococci". Antimicrobial Agents and Chemotherapy. 61 (3): e01422–16, /aac/61/3/e01422–16.atom. doi:10.1128/AAC.01422-16. PMC   5328519 . PMID   28069645.
  13. ↑ Commichau FM, Gibhardt J, Halbedel S, Gundlach J, Stülke J (March 2018). "A Delicate Connection: c-di-AMP Affects Cell Integrity by Controlling Osmolyte Transport". Trends in Microbiology. 26 (3): 175–185. doi:10.1016/j.tim.2017.09.003. PMID   28965724.
  14. ↑ Zhang L, Li W, He ZG (February 2013). "DarR, a TetR-like transcriptional factor, is a cyclic di-AMP-responsive repressor in Mycobacterium smegmatis". The Journal of Biological Chemistry. 288 (5): 3085–96. doi: 10.1074/jbc.M112.428110 . PMC   3561532 . PMID   23250743.
  15. ↑ Corrigan RM, Campeotto I, Jeganathan T, Roelofs KG, Lee VT, Gründling A (May 2013). "Systematic identification of conserved bacterial c-di-AMP receptor proteins". Proceedings of the National Academy of Sciences of the United States of America. 110 (22): 9084–9. Bibcode:2013PNAS..110.9084C. doi: 10.1073/pnas.1300595110 . PMC   3670340 . PMID   23671116.
  16. ↑ Mehne FM, Gunka K, Eilers H, Herzberg C, Kaever V, Stülke J (January 2013). "Cyclic di-AMP homeostasis in bacillus subtilis: both lack and high level accumulation of the nucleotide are detrimental for cell growth". The Journal of Biological Chemistry. 288 (3): 2004–17. doi: 10.1074/jbc.M112.395491 . PMC   3548507 . PMID   23192352.
  17. 1 2 Luo Y, Helmann JD (February 2012). "Analysis of the role of Bacillus subtilis σ(M) in β-lactam resistance reveals an essential role for c-di-AMP in peptidoglycan homeostasis". Molecular Microbiology. 83 (3): 623–39. doi:10.1111/j.1365-2958.2011.07953.x. PMC   3306796 . PMID   22211522.
  18. ↑ Witte CE, Whiteley AT, Burke TP, Sauer JD, Portnoy DA, Woodward JJ (May 2013). Mekalanos J (ed.). "Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infection". mBio. 4 (3): e00282-13. doi:10.1128/mBio.00282-13. PMC   3663569 . PMID   23716572.
  19. ↑ Corrigan RM, Bowman L, Willis AR, Kaever V, Gründling A (February 2015). "Cross-talk between two nucleotide-signaling pathways in Staphylococcus aureus". The Journal of Biological Chemistry. 290 (9): 5826–39. doi: 10.1074/jbc.M114.598300 . PMC   4342491 . PMID   25575594.
  20. ↑ Jin L, Hill KK, Filak H, Mogan J, Knowles H, Zhang B, et al. (September 2011). "MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP". Journal of Immunology. 187 (5): 2595–601. doi:10.4049/jimmunol.1100088. PMC   3159690 . PMID   21813776.
  21. ↑ Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B, Hyodo M, et al. (September 2011). "STING is a direct innate immune sensor of cyclic di-GMP". Nature. 478 (7370): 515–8. Bibcode:2011Natur.478..515B. doi:10.1038/nature10429. PMC   3203314 . PMID   21947006.
  22. ↑ Škrnjug I, Rueckert C, Libanova R, Lienenklaus S, Weiss S, Guzmán CA (2014-04-22). "The mucosal adjuvant cyclic di-AMP exerts immune stimulatory effects on dendritic cells and macrophages". PLOS ONE. 9 (4): e95728. Bibcode:2014PLoSO...995728S. doi: 10.1371/journal.pone.0095728 . PMC   3996008 . PMID   24755640.
  23. ↑ Parvatiyar K, Zhang Z, Teles RM, Ouyang S, Jiang Y, Iyer SS, et al. (December 2012). "The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response". Nature Immunology. 13 (12): 1155–61. doi:10.1038/ni.2460. PMC   3501571 . PMID   23142775.
  24. 1 2 Ergun SL, Fernandez D, Weiss TM, Li L (July 2019). "STING Polymer Structure Reveals Mechanisms for Activation, Hyperactivation, and Inhibition". Cell. 178 (2): 290–301.e10. doi: 10.1016/j.cell.2019.05.036 . PMID   31230712.
  25. ↑ Barker JR, Koestler BJ, Carpenter VK, Burdette DL, Waters CM, Vance RE, Valdivia RH (April 2013). Taylor R (ed.). "STING-dependent recognition of cyclic di-AMP mediates type I interferon responses during Chlamydia trachomatis infection". mBio. 4 (3): e00018-13. doi:10.1128/mBio.00018-13. PMC   3663186 . PMID   23631912.
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